Selective synthesis of carvone and cryptomerlone from α-pinene

Article abstract of DOI:10.1007/s10600-006-0104-8

Carvone and cryptomerlone were synthesized selectively using electrochemical oxidation of α-pinene in the key step. 2006 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10600-006-0104-8

Chemistry of Natural Compounds, Vol. 42, No. 3, 2006
SELECTIVE SYNTHESIS OF CARVONE AND
CRYPTOMERLONE FROM
α-PINENE
F. Macaev, L. Vlad, and A. Gudima
UDC 547.596/598
Carvone and cryptomerlone were synthesized selectively using electrochemical oxidation of α-pinene in the
key step.
Key words: mono- and sesquiterpenoids, α-pinene, carvone, cryptomerlone, electrochemical oxidation.
The use of Pt or RuO /TiO anodes and an electrolyte (AcOH-AcONa—NaClO ) for electrochemical oxidation of
2
2
4
α-pinene (1) has been previously reported [1].
We investigated anodic oxidation of α-pinene using Ac O in combination with AcOH-AcONa and carbon electrodes.
2
The reaction product was predominantly a mixture of two compounds that could be isolated by chromatography and
characterized.
The less polar product was eluted from a SiO column and turned out to be carveol acetate 2. The more polar
2
compound eluted from the column was sobrerol diacetate (3). Ester 3 eliminates AcOHon boiling in Ac O toform an additional
2
amount of 2.
c
RO
AcO
O
a
+
OAc
1
2, 4
3
5
2: R = Ac
4: R = H
b
d
-
a.
b.
c.
d.
Ac2O, AcOH, AcONa, e ; 10% NaOH, EtOH; Ac2O, boiling 8 h; MnO2
Electrochemical oxidation of 1 was also carried out using carbon electrodes in AcOH-AcONa [2]. However, the yield
of 4 was less than 12%.
Hydrolysis of 2 gave in high yield alcohol 4, oxidation of which by MnO in CH Cl led to carvone 5, which was
2
2
2
identified by its spectral and chromatographic properties compared with an authentic sample.
Silyl ether ofcarveol 6 was brominated using NBS in benzene to give 7. Its IR spectrum contained bands characteristic
-1
-1
of siloxy (1265 cm ) and a trisubstituted double bond (1650 cm ). Its PMR spectrum contained a multiplet at 0.54-2.67 ppm
for protons of ethyls on Si, a methyl, and two methylenes. Furthermore, signals for a methylene on Br were observed at
3.77 ppm. The allyl proton H-6 resonated at 4.03 ppm. Broadened signals of vinyls H-9 and H-2 appeared at 4.73 and
5.50 ppm, respectively.
Bromide 7 reacted with 3-methyl-2-butenylmagnesium bromide in the presence of CuBr to form triene 8. Removal
of the silyl protection and subsequent treatment with PDC completed the synthesis of cryptomerlone 9, the spectral properties
of which agreed with those in the literature [3].
Institute of Chemistry, Academy of Sciences of Moldova, ul. Akademicheskaya, 3, Kishinev, MD-2028, Republic of
Moldova, fax (37322) 73 97 75, e-mail: flmacaev@cc.acad.md. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp.
248-250, May-June, 2006. Original article submitted April 24. 2006.
0009-3130/06/4203-0301 ©2006 Springer Science+Business Media, Inc.
301

7
1
Et SiO
3
HO
Et SiO
3
O
Et SiO
3
d, e
a
c
b
3
5
13
11
8
Br
14
9
12
4
6
7
8
9
a. Et3SiCl, Im; b. NBS; c. Grignard reagent, CuBr, THF; d. AcOH/THF/H2O; e. PDC
Thus, we carried out a specific synthesis of carvone and cryptomerlone using electrochemical oxidation of α-pinene
to construct the p-menthane fragment of the target products.
EXPERIMENTAL
13
IR spectra were recorded on a Specord 75 spectrophotometer; PMR and C NMRspectra, on Bruker AC-E200 (200.13
and 50.32 MHz) and Bruker AC-80 (80 and 20 MHz) spectrometers for CDCl solutions (2-3%) with TMS internal standard.
3
Specific rotation was measured on a Perkin-Elmer 241 polarimeter. Column chromatography used SiO L40/100, 100/160 µ
2
(Czech Rep.) and 40/63 µ (Fluka); TLC, Silufol plates (Czech Rep.) developed using phosphomolybdic acid in EtOH (5%) with
subsequent heating or acidification with aqueous KMnO (2%).
4
Analytical data of all synthesized compounds agreed with those calculated.
20
20
Starting α-pinene (1, Fluka) was a mixture of enantiomers with n
1.466, [α]
-45° (l = 1, pure).
D
D
Electrochemical Oxidation of α-Pinene. Compound 1 (15.44 g, 113.5 mmol), Ac O (50 mL), AcOH (1 mL), and
2
AcONa (0.4 g) were placed in a 30-mm diameter cylinder. Two graphite electrodes (10-mm diameter) were inserted with a
distance of 5 mm between them. Electrical current (100 mA) was passed for 120 h. The reaction mixture was poured into
saturated NaCl solution (250 mL), treated with saturated NaHCO solution (100 mL), left for 3 d, extracted with CHCl
3
3
(4 × 100 mL), and washed with water (100 mL) and saturated NaHCO solution (3 × 100 mL). The combined extracts were
3
dried over anhydrous Na SO . The solvent was distilled off to afford a solid (18.8 g) that was charmatographed over SiO with
2
4
2
elution by ethylacetate:petroleum ether (1:20) to give 4 (6.5 g, 30%) and 6 (6.7 g, 23%).
20
-1
Mixture of Diastereomers 2. n
1.4715. IR spectrum (mineral oil, ν, cm ): 1380, 1735 (OAc), 1650 (=CH ).
2
D
PMR spectrum of the predominant isomer (200 MHz, CDCl , δ, ppm, J/Hz): 1.17-2.19 (5H, m, H-4, H-3, H-5), 1.63,
3
1.66 (6H, 2 s, H-7, H-10), 1.99 (3H, s, H-Ac), 4.61-4.67 (2H, m, H-9), 5.15 (1H, m, H-6), 5.55 (1H, m, H-2).
13
C NMRofthe predominant isomer (50 MHz, CDCl ): 16.59 (C-7), 20.39 (C-10), 20.61 (COMe), 30.73 (C-3), 33.52
3
(C-4), 40.13 (C-5), 70.39 (C-6), 109.04 (C-9), 127.60 (C-2), 130.79 (C-1), 148.42 (C-8), 170.54 (COMe).
20
-1
Mixture of Diastereomers 3. n
1.4660. IR spectrum (mineral oil, ν, cm ): 1385, 1720 (OAc), 1670 (C=CH).
D
PMR spectrum ofthe predominant isomer (200 MHz, CDCl , δ, ppm, J/Hz): 1.18, 1.19 (6H, 2 s, H-9, H-10), 1.43-1.56
3
(1H, m, H-4), 1.62 (3H, s, H-7), 1.70-2.30 (4H, m, H-3, H-5), 1.93, 2.04 (6H, 2 s, 2 Ac), 5.15 (1H, m, H-6), 5.64 (1H, m, H-2).
13
C NMR spectrum of the predominant isomer (50 MHz, CDCl ): 18.29 (C-7), 22.00, 20.94 (2COMe), 22.61 (C-10),
3
23.16 (C-9), 26.20 (C-3), 29.78 (C-5), 37.18 (C-4), 70.37 (C-6), 83.35 (C-8), 127.23 (C-2), 130.63 (C-1), 170.57, 169.85
(2COMe).
Mixture of Diastereomers 4. A solution of NaOH (0.48 g, 12 mmol) in ethanol (30 mL) was stirred and treated with
2 (0.93 g, 4.79 mmol), stirred for 48 h, diluted with saturated NaCl solution (60 mL), and extracted with ether (4 × 25 mL).
The ether extract was washed with saturated NaCl solution and dried over anhydrous Na SO . Solvent was distilled offtoafford
2
4
20
4 (0.63 g, 95%), n
1.4945.
D
-1
IR spectrum (mineral oil, ν, cm ): 3390 (OH), 1650 (=CH ).
2
PMR spectrum of the predominant isomer (80 MHz, CDCl , δ, ppm, J/Hz): 0.91-2.34 (11H, m, H-10, H-7, H-3, H-5,
3
H-4), 4.06 (1H, m, H-6), 4.78 (2H, m, H-9), 5.59 (1H, m, H-2).
13
C NMRspectrum ofthe predominant isomer (20 MHz, CDCl ): 18.81 (C-7), 20.68 (C-10), 30.82 (C-3), 36.53 (C-4),
3
40.37 (C-5), 70.56 (C-6), 108.76 (C-9), 125.02 (C-2), 134.12 (C-1), 149.00 (C-8).
302

Carvone 5. A solution of 4 (0.69 g, 4.54 mmol) in anhydrous CH Cl (50 mL) was stirred and treated in portions with
2
2
MnO (25 g, 5 g portions) over 24 h. The MnO was filtered off and washed with CH Cl . The combined extract was
2
2
2
2
20
20
evaporated to afford 5 (0.42 g, 70%), n
1.4961, [α]
-1.5° (c 1.1, CHCl ).
3
D
D
-1
IR spectrum (mineral oil, ν, cm ): 1715 (C=O), 1645 (=CH ).
2
PMR spectrum (80 MHz, CDCl , δ, ppm, J/Hz): 1.56 (6H, br. s, H-7, H-10), 2.07-2.53 (5H, m, H-3, H-5, H-4),
3
4.60-4.65 (2H, m, H-9), 6.59 (1H, m, H-2).
13
C NMRspectrum (20 MHz, CDCl ): 15.48 (C-7), 20.30 (C-10), 31.04 (C-3), 42.28 (C-4), 42.94 (C-5), 110.26 (C-9),
3
135.30 (C-1), 144.37 (C-2), 146.47 (C-8), 199.43 (C-6).
Mixture of Diastereomers 6. A solution of 4 (1 g, 6.57 mmol) and imidazole (0.48 g, 7.05 mmol) in anhydrous
CH Cl (20 mL) was stirred and treated with Et SiCl (1.06 g, 7.05 mmol) and left overnight. The solid was filtered off.
2
2
3
The solvent was evaporated. The solid was chromatographed over SiO with elution by hexane to afford a light yellow oil (6,
2
1.62 g), yield 87%.
-1
IR spectrum (mineral oil, ν, cm ): 1260 (C–O–Si), 1660 (=CH ).
2
PMR spectrum of the predominant isomer (80 MHz, CDCl , δ, ppm, J/Hz): 0.46-2.31 (26H, m, H-Et , H-7, H-10, H-3,
3
3
H-5, H-4), 4.25 (1H, m, H-6), 4.71 (2H, m, H-9), 5.45 (1H, m, H-2).
13
C NMR spectrum of the predominant isomer (20 MHz, CDCl ): 5.07 [Si(CH CH ) ], 6.91 [Si(CH CH ) )], 19.46
3
2
3 3
2
3 3
(C-7), 20.31 (C-10), 31.08 (C-3), 38.63 (C-4), 40.95 (C-5), 71.43 (C-6), 108.93 (C-9), 123.43(C-2), 136.92(C-1), 149.12(C-8).
Mixture of Diastereomers 7. A mixture of 6 (0.8 g, 3 mmol), NBS (0.56 g, 3.15 mmol), and benzoyl peroxide
(0.02 g) in CCl (10 mL) was boiled for 4 h. The solid was washed with CCl . The combined filtrate was washed with saturated
4
4
NaCl solution (3 × 5 mL) and dried over anhydrous Na SO . Solvent was distilled. The solid was chromatographed over SiO
2
2
4
(hexane eluent) to afford an unstable yellow oily product (7, 0.46 g), yield 44%.
-1
IR spectrum (mineral oil, ν, cm ): 580 (C–Br), 1265 (C–O–Si), 1650 (=CH ).
2
PMR spectrum of the predominant isomer (80 MHz, CDCl , δ, ppm, J/Hz): 0.54-2.67 (23H, m, H-7, H-3, H-5, H-4),
3
3.77 (2H, s, H-10), 4.03 (1H, m, H-6), 4.73 (2H, m, H-9), 5.50 (1H, m, H-2).
Mixture of Diastereomers 8. A solution of 3-methyl-2-butenylmagnesium bromide in dry THF (10 mL), prepared
from 3-bromo-2-methyl-2-butene (0.592 g, 4 mmol) and Mg (0.3 g), was added dropwise with stirring to a cold (icewater)
solution of 7 (1.06 g, 4 mmol) and CuBr (25 mg). The mixture was stirred for an additional 6 h, left overnight at room
temperature, treated with saturated NH Cl solution (10 mL), extracted with ether, and dried over anhydrous Na SO . Solvent
4
2
4
was evaporated to afford 8 (1.15 g), which was used without further purification.
PMR spectrum of the predominant isomer (80 MHz, CDCl , δ, ppm, J/Hz): 0.34-1.08 (15H, m, H-Et ), 1.63 (3H, br.
3
3
s, H-7), 1.83-1.85 (6H, m, H-13, H-14), 3.89-4.01 (1H, m, H-6), 5.50-5.89 (4H, H-2, H-9, H-12).
Cryptomerlone 9. A solution of 8 (1.15 g, 3.44 mmol) in THF (5 mL) was treated dropwise with aqueous AcOH
(10 mL, 50%). The mixture was stirred for 8 h, extracted with ether (3 × 50 mL), and dried over anhydrous Na SO . Solvent
2
4
was distilled. The solid was dissolved in CH Cl (5 mL), treated with cooling (icewater) with pyridinium dichlorochromate
2
2
(PDC) (720 mg), stirred for 14 h, treated with H O (10 mL), extracted with CH Cl (3 × 25 mL), washed with saturated NaCl
2
2
2
solution, and dried over anhydrous Na SO . Solvent was evaporated. The solid was chromatographed over SiO to afford a
2
4
2
20
20
20
colorless liquid (9, 134 mg), yield 20% calculated for 8, n
1.5035, [α]
-4.0° (c 0.2, CHCl ), lit. [3]: n
D
1.5041.
D
D
3
ACKNOWLEDGMENT
We thank Prof. A. G. Yurchenko and A. De Groot for help with recording the NMR spectra and specific rotation and
helpful discussions of the results.
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