Reaction of elemol with acetic acid/perchloric acid: Characterization of a novel oxide and (+)-β-cyperone

Article abstract of DOI:10.1002/hlca.200690050

The minor unidentified compounds of the acetic acid/perchloric acid dehydration of elemol (1) were fully characterized. The structure and relative configuration of the less polar fragrant compound 2, named elemoxide, was deduced by ID- and 2D-NMR data inc

Full text of DOI:10.1002/hlca.200690050

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Helvetica Chimica Acta – Vol. 89 (2006)
Reaction of Elemol with Acetic Acid/Perchloric Acid: Characterization of a
Novel Oxide and (+)-b-Cyperone
by Solimabi Wahidulla*, Mangala Babu Govenkar, and Sashikumar Keshav Paknikar
National Institute of Oceanography, Dona Paula-403004, Goa, India
(fax: +91-(0) 832-2450603, 2450604; e-mail: solima@darya.nio.org)
The minor unidentified compounds of the acetic acid/perchloric acid dehydration of elemol (1) were
fully characterized. The structure and relative configuration of the less polar fragrant compound 2,
named elemoxide, was deduced by 1D- and 2D-NMR data including C,C-connectivity, NOE, and
NOESY experiments. The absolute configuration was established as (3S,3aR,7aR)-1,3,3a,4,7,7a-hexahy-
dro-6-isopropyl-1,1,3,3a-tetramethylisobenzofuran (2) on the basis of its preparation from elemol (1).
(+)-b-cyperone (3), a known sesquiterpene, was also identified as a minor product of the reaction. A
plausible mechanistic explanation for the formation of elemoxide (2) and (+)-b-cyperone (3) is pre-
sented.
Introduction. – The structure of the major product a-elemene (4) [1][2], obtained
by reaction of elemol (1) with AcOH/HClO4, was established beyond doubt by chem-
ical correlation studies [1]. The assigned structure recently received further confirma-
tion by Mehta and Acharyulu [3]. Besides the a- and d-elemenes (4 and 5, resp.) [2], the
reaction mixture contained an uncharacterized fragrant substance 2 (Scheme 1)1). We
report herein the structure of this component, now called elemoxide (2), and the iden-
tification of a more polar product as (+)-b-cyperone (3).
GC/CI-MS Analysis of the reaction product obtained from 1 revealed the presence
of four stereoisomers, including 2, with the retention time tR 19.6, 20.5, 26.1, and 27.2
min and a % area of 6.48, 8.26, 15.19, and 21.56, respectively. Identification was
based on the molecular ion [M+H]+ and the fragmentation pattern observed in the
MS. NMR did not show the presence of regioisomers.
Results and Discussion. – Elemoxide (2), obtained as an optically active light yellow
oil, displayed a molecular ion M+ at m/z 222 in its EI-MS confirming the molecular for-
mula C15H26O. The IR spectrum displayed an absorption at 1068 cmÀ1 due to an ether
linkage; the absorptions at 1640 and 808 cmÀ1 were attributed to a trisubstituted C=C
bond, and a geminal dimethyl moiety was evident from a doublet at 1365 and 1377
1
1
cmÀ1. Detailed analysis of the NMR data, in particular the H,1H-COSY, H,13C-
HSQC, and HMBC data, allowed us to secure the entire hydrocarbon framework of
structure 2 as well as the 1H- and 13C-NMR assignments (Table).
1
)
For convenience, the side chains are arbitrarily numbered.
© 2006 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 89 (2006)
497
Scheme 1
Table. 1H- and 13C-NMR, and COSY Data of Elemoxide (2) in CDCl3. d in ppm, J in Hz.
13C-NMR 1H-NMR
1H,1H-COSY 1H,13C-HMBC
NOESY
C(1)
78.7 (s)
–
–
–
–
HÀC(3)
81.2 (d) 3.55 (q,
J=6.3)
Me(8)
C(9), C(4), C(7a)
Me(11), Me(8), CH2(4),
HÀC(7a)
C(3a)
CH2(4)
42.7 (s)
37.7 (t)
–
–
–
–
–
1.9 (s)
1.72 (d,
J=5.1)
HÀC(5)
C(6), C(9), C(7a)
C(6), C(9), C(7a)
HÀC(5), HÀC(3)
HÀC(5)
HÀC(5), Me(9)
HÀC(5)
117.7 (d) 5.36 (d,
J=4.5)
CH2(4)
C(3a), C(7), C(12)
HÀC(12), CH2(4), Me(13)
C(6)
CH2(7)
143.4 (s)
23.9 (t)
–
–
–
–
1.89 (d,
J=3.3)
HÀC(7a)
C(5), C(3a)
HÀC(12), HÀC(7a)
HÀC(7a) 54.3 (d) 1.75 (t,
CH2(7)
C(4), C(10), C(9),
C(11), C(6)
C(3a)
Me(11), CH2(7), HÀC(3)
J=5.4)
Me(8)1)
Me(9)1)
14.4 (q) 1.13 (d,
J=6.3)
12.6 (q) 0.77 (s)
HÀC(3)
CH2(4), Me(9)
–
–
C(4), C(7a), C(3)
C(11), C(7a)
C(10), C(7a)
C(5)
CH2(7), CH2(4), Me(8)
–
Me(10)1) 24.8 (q) 1.16 (s)
Me(11)1) 30.6 (q) 1.24 (s)
HÀC(12)1) 35.2 (d) 2.18–2.29
(m)
HÀC(7a)
Me(13)
CH2(7), Me(13), HÀC(5)
Me(13)1) 21.4 (q) 1.02 (d,
J=7.92)
HÀC(12)
HÀC(12)
C(6), C(14)
C(6), C(14)
HÀC(12), CH2(7)
HÀC(12), CH2(7)
Me(14)1) 21.9 (q) 1.04 (d,
J=7.92)

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The relative configuration of 2 was inferred on the basis of NOESY and NOE dif-
ference spectra. Since the absolute configuration of elemol (1) is known [4][5], the
absolute configuration of the oxide was established as (3S,3aR,7aR)-1,3,3a,4,7,7a-hexa-
hydro-6-isopropyl-1,1,3,3a-tetramethylisobenzofuran (2). The probable pathway for
the formation of elemoxide (2) from elemol (1) is shown in Scheme 2.
Scheme 2. Formation of Elemoxide (2) from Elemol (1)
The 1H-NMR spectrum of 2 showed signals for an olefinic H-atom at d 5.36 (d, J=4.5 Hz), a OCH
moiety at d 3.55 (q, J=6.3 Hz) and a CH group centered at d 2.26 (m). In the upfield region appeared
signals for three tertiary Me groups centered at d 1.24 (s), 1.16 (s), and 0.77 (s), for isopropyl Me groups
centered at d 1.03 (d, J=7.92 Hz, 6 H) and for a secondary Me group at d 1.13 (d, J=7.2 Hz).
The 13C-NMR spectrum (Table) revealed signals for 15 C-atoms that, on the basis of DEPT experi-
ments, were indicative of 6 Me, 2 CH2, and 4 CH groups (including an olefinic and a O-bearing CH), and
3 quarternary C-atoms. The low-field signals revealed the trisubstituted nature of the C=C bond at d
143.4 and 117.7.
In the 1H,1H-COSY spectrum, the correlations of HÀC(5) at d 5.36 with CH2(4) at d 1.9 and 1.72, of
HÀC(3) at d 3.55 with Me(8) at 1.13, of HÀC(12) at d 2.26 with Me(13) and Me(14) at d 1.03, and of HÀ
C(7a) at d 1.75 with CH2(7) at d 1.89 were clearly observed1). The 2- or 3-bond 1H,13C-HMBC correla-
tions of the olefinic HÀC(5) at d 5.36 with C(7), C(12), and C(3a) and of CH2(4) with C(6), C(7a), and
C(9) established the presence of a pentahydro-isopropyl-methylbenzene moiety. The 1H,13C-HMBC cor-
relations HÀC(3)/C(7a), HÀC(9)/C(7a), Me(10)/C(7a), and Me(11)/C(7a) suggested the inclusion of the
benzene system in a isobenzofuran moiety. These correlations in conjunction with the 1H,1H-COSY data
established the gross structure of 2 to be 1,3,3a,4,7,7a-hexahydro-6-isopropyl-1,1,3,3a-tetramethyl-
isobenzofuran. The position of the C=C bond was confirmed by decoupling experiments: on selective
irradiation of the olefinic signal at d 5.36, the signal at d 1.72 collapsed to a broad s. A NOESY relation-
ship between HÀC(3) at d 3.55 and HÀC(7a) at d 1.75 suggested trans configuration at the fusion site
C(3a)ÀC(7a) and a trans relationship of MeÀC(3a) and HÀC(3). The NOESY correlation observed
between Me(8) (=MeÀC(3a)) and Me(9) indicated that they are cis to each other. Thus the b configu-
ration of MeÀC(3a) and the a-configuration of HÀC(7a) present in natural elemol (1) has remained
unchanged during the conversion to the tetrahydrofuran derivative.
The more polar compound 3 of molecular formula C15H22O showed in its IR spec-
trum the presence of an a,b unsaturated ketone moiety (1658, 1618 cmÀ1). Comparison
of all spectral data of 3 with published data for (+)-b-cyperone [6–12] showed an excel-
lent agreement. The spectral data of the (2,4-dinitrophenyl)hydrazone derivative of 3
was also in accordance with the literature values [13][14].
The 13C- and DEPT-NMR data of 3 indicated the presence of 4 Me, 4 CH2, and 2 CH groups, of which
one was an olefinic CH, and 5 quartenary C-atoms. Thus, 3 must be bicyclic. The 1H-NMR spectrum con-
firmed the above conclusion. Two 3-H s at d 1.11 and 1.87 were assigned to the angular Me group and a

Helvetica Chimica Acta – Vol. 89 (2006)
499
Me group in a position to a carbonyl group as a part of the conjugated ketone system. The presence of an
isopropyl group and an olefinic proton was evident from the d at d 1.084 (J=2.1 Hz) and a s at d 6.29,
respectively.
The formation of (+)-b-cyperone (3) from elemol (1) can be explained by acid cat-
alyzed dehydration of 1 to d-elemene (5) which in turn is transformed to the eudesmane
hydrocarbon d-selinene (=2,3,4,4a,5,6-hexahydro-7-isopropyl-1,4a-dimethylnaphtha-
lene) [15]. While carrying out the reaction, oxygen was not excluded from the mixture.
An oxidation of these hydrocarbons would finally afford (+)-b-cyperone (3) as outlined
in (Scheme 3).
Scheme 3. Formation of (+)-b-Cyperone (3) from Elemol (1)
Conclusions. – In summary, we have described the novel fragrant sesquiterpene
oxide 2 and the known (+)-b-cyperone (3) as minor products of the dehydration of ele-
mol (1). The novel oxide is multiodorant being a combination of rhubarb, laurel, thyme,
and florex. Both compounds were identified on the basis of their extensive NMR spec-
troscopic data. A mechanism for their formation from 1 is also discussed.
The authors wish to thank Dr. S. R. Shetye, Director NIO for his keen interest in the work and con-
stant encouragement. Our special thanks are due to Dr. B. Maurer of Firmenich SA, Geneva, for some of
the spectra and valuable comments. We are also grateful to Mr. Ramakant Harlalkar, for the generous gift
of an elemol-rich fraction of Java citronella oil. One of the authors (M. G.) wishes to thank CSIR for the
award of JRF. NIO contribution number is 4058.
Experimental Part
1. General. Anal. TLC: precoated 0.25 mm Merck silica gel G60 F254 aluminium sheets; visualization
by spraying with 5% H2SO4/MeOH. Column chromatography (CC): silica gel (60–120 mesh; Qualigens).
Melting points (m.p.): Electrothermal 91. Optical rotations: optical polarimeter ADP 220 (Bellingham
Stanley Ltd.); in CHCl3. IR Spectra: Shimadzu FT-IR-8201-PC spectrometer; KBr pellets. NMR Spectra
(1H, 13C, COSY, HMQC, and HMBC): 300-MHz Bruker Avance-300 spectrometer. CDCl3 soln. contain-
ing SiMe4 as the internal standard. EI-MS: at 70 eV. GC/MS: Shimadzu 2010 gas chromatograph fitted

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with a XTI-5 (bonded, 5% phenyl) capillary column (30 m×0.32 mm; film thickness 0.25 mm) and cou-
pled to a Shimadzu 2010 mass selective detector; oven temp. was programmed from 608 at 58/min; He as
carrier gas at a flow rate of 1.8 ml/min; ion-source temp. 2008, interface temp. 2208, solvent cut time 2
min, and detector voltage 1 kV; scanning from m/z 60 to 400 for 85 min; PCI mode for analysis with iso-
butane as the reagent gas.
2. Purification of Elemol (1). The higher boiling fraction of Java citronella oil (supplied by Nishant
Aromas, Mumbai) was subjected to CC (SiO2, gradient petroleum ether/AcOEt). The fraction eluted
with petroleum ether/AcOEt 95 :5 furnished 1. Colorless crystals (MeOH). M.p. 528 ([1]: 538). Rf
(AcOEt/light petroleum ether 8 :92) 0.5. [a]D =À4.73 (c=2.3, CHCl3).
3. Dehydration of Elemol (1). To a soln. of 1 (3.5 g) in AcOH (42 ml), 60% perchloric acid (0.7 ml)
was added dropwise, and the mixture was left at 25–278 for 72 h with stirring. The dark brown soln. was
diluted with H2O and extracted with Et2O, the Et2O layer washed free from acid, dried, and evaporated,
and the residue subjected to careful CC (silica gel). Besides a-elemene (4) and d-elemene (5), 0.28 g (8%)
of 2 was obtained (with AcOEt/light petroleum ether 4 :96) and 0.12 g (3.4%) of 3 (with AcOEt/light
petroleum ether 5 :95; after purification by repeated CC (silica gel)).
Data of Elemoxide (=(3S,4aR,7aR)-1,3,3a,4,7,7a-hexahydro-6-isopropyl-1,1,3,3a-tetramethylisoben-
zofuran; 2): Rf (AcOEt/light petroleum ether 4 :96) 0.6. [a]D =À57.2 (c=1.1, EtOH). IR (KBr): 2964,
1640, 1377, 1365, 1184, 1068, 950, 808, 777. 1H- and 13C-NMR: Table. EI-MS: 222(14.4), 207(30.2),
178(14.4), 163(32.4), 149(10.8), 135(74.8), 121(46), 107(44), 93(100), 79(18), 43(43).
Data of (+)-b-Cyperone (=(4aS)-4,4a,5,6-Tetrahydro-7-isopropyl-1,4a-dimethylnaphthalen-2(3H)-
one; 3): Rf (AcOEt/light-petroleum ether 6 :94) 0.4. [a]D =+365 (c=1.5, CHCl3). IR (neat): 2925,
1658, 1618, 1323, 1288. 1H-NMR: 6.29 (d, J=2.1, HÀC(8)); 2.7–2.1 (m, CH2(3), CH2(6), Me2CH);
1.87 (br. s, MeÀC(1)); 1.78–1.5 (m, 4 H); 1.11 (s, MeÀC(4a)); 1.084 (d, J=2.1, Me2CH). 13C-NMR:
199.2 (s, C(2)); 156.2 (s, C(1)); 156.0 (s, C(8a)); 126.35 (s, C(7)); 118.2 (d, C(8)); 37.1 (t, C(4)); 36.4 (t,
C(5)); 36.1 (d, Me2CH); 33.8 (t, C(3)); 33.2 (s, C(4a)); 23.7 (t, C(6)); 21.5 (q, MeCHMe); 21.0 (q,
MeCHMe, MeÀC(4a)); 10.1 (q, MeÀC(1)). EI-MS: 218 (25, M+), 203 (43), 175 (47), 147 (21), 119
(32), 91 (100).
5. 2,4-Dinitrophenylhydrazone of 3. To a soln. of 2,4-nitrophenylhydrazine (50 mg) in MeOH (5 ml),
3 drops of conc. HCl soln. were added, followed by 3 (120 mg) in MeOH. The mixture was allowed to
stand for a few minutes. Then, the formed red precipitate was filtered and purified by CC (silica gel,
AcOEt/light petroleum ether 1:9): bright red needles. M.p. 216–2188 ([13]: 2188). [a]D =+721
(c=0.6, CHCl3). Rf (AcOEt/light petroleum ether 1:9) 0.6. IR (KBr): 3311, 2927, 1618, 1591, 1500,
1
1336, 1309. H-NMR: 11.3 (s, 1 H); 9.13 (d, J=3, 1 H); 8.05 (d, J=7.5, 1 H); 8.3 (dd, J=7.5, 3, 1 H);
6.4 (s, 1 H); 1.0 (s, 3 H); 1.118 (d, J=6.9, 6 H); 2.08 (s, 3 H). 13C-NMR: 155.8 (s); 144.7 (s); 147.8 (s);
152.2 (s); 129.9 (d); 129.5 (s); 123.6 (d); 117.9 (d); 32.7 (s); 23.5 (t); 21.6 (t); 21.6 (q); 21.2 (q). EI-MS:
398 (100, M+), 383 (22), 364 (5), 349 (6), 321 (6), 307 (1), 216 (5), 200 (8), 186 (3), 172 (5), 157 (10),
131 (12), 105 (15), 91 (21).
REFERENCES
[1] S. K. Paknikar, S. C. Bhattacharya, Tetrahedron 1962, 18, 1509.
[2] N. Akira, M. Michio, T. Haruki, Y. Toshio, JP 54084551, 1979.
[3] G. Mehta, P. V. R. Acharyulu, J. Ind. Chem. Soc. 1998, 75, 601.
[4] T. G. Halsall, D. W. Theobold, K. B. Walshaw, J. Chem. Soc. 1964, 1029.
[5] A. D. Wagh, S. K. Paknikar, S. C. Bhattacharya, Tetrahedron 1964, 20, 2647.
[6] P. S. Adamson, F. J. McQuillin, R. Robinson, J. L. Simonsen, J. Chem. Soc. 1937, 1576.
[7] H. Bruderer, D. Arigoni, O. Jeger, Helv. Chim. Acta 1956, 39, 858.
[8] D. H. R. Barton, E. J. Tarlton, J. Chem. Soc. 1954, 3492.
[9] R. Howe, F. J. McQuillin, J. Chem. Soc. 1955, 2423.
[10] R. B. Gammil, T. A. Bryson, Synth. Commun. 1976, 6, 209.
[11] B. Gonzalo, L. Cardona, B. Garcia, L. G. Cristina, J. R. Pedro, Tetrahedron 1996, 52, 10507.
[12] G. Z. Z. Xiong, Y. Chen, Y. Li, J. Chem. Res. (S) 1998, 650.
[13] A. E. Bradfield, B. H. Hedge, B. Sanjiva Rao, J. L. Simonsen, A. E. Gillam, J. Chem. Soc. 1936, 667.

Helvetica Chimica Acta – Vol. 89 (2006)
501
[14] J. P. Kutney, J. Balsevich, P. Grice, Can. J. Chem. 1980, 58, 2641.
[15] D. P. Piet, A. J. Minnard, K. A. Van der Heyden, C. R. Fransen Maurice, J. B. P. A. Wijinberg, A. De
Groot, Tetrahedron 1995, 51, 243.
Received October 6, 2005