3.2. Preparation of Epoxycarvone Stereoisomers
The oily compounds were prepared in our laboratory according to the literature [
27,
28,
29,
30]. The
1H- and
13C-NMR measurements were obtained with a Mercury-Varian spectrometer (Palo Alto, CA, USA) operating at 200 MHz (for
1H), and 50 MHz (for
13C). The infrared spectra were recorded on a Bomen Michelson model 102 FTIR (Bomen, Chicago, IL, USA) and the most intense or representative bands reported (in cm
−1). Optical rotations were measured on an Optical Activity AA-10 automatic polarimeter (Optical Activity Limited, Ramsey, UK) at ambient temperature.
3.2.1. Reduction of (−)-Carvone (1) and (+)-Carvone (2)
Sodium borohydride (2.5 g, 66.1 mmol) was added at 20 °C to a solution of
1 or
2 (10 g, 67 mmol), and CeCl
3·7H
2O (25 g, 148.5 mmol) in methanol (500 mL). The mixture was stirred for 5 min. Then, diethyl ether (100 mL) and water (100 mL) were added. The organic layer was separated, and the aqueous layer was extracted with diethyl ether (3 × 100 mL). The organic layers were combined and dried over Na
2SO
4, and filtered. The filtrate was concentrated under reduced pressure, and the residue was subjected to column chromatography on silica gel using a mixture of ethyl hexane and ethyl acetate (8:2) as eleuent. (−)-
cis-Carveol (
3) and (+)-
cis-carveol (
4) were obtained with 80% (53.46 mmol) and 78% (52.0 mmol) yields, respectively [
27,
28].
(3): = −33.7 (CHCl3, c 0.03); IR (KBr) νmax: 3461, 2945, 2900, 1650, 1500, 1050, 900 cm–1; 1H-NMR (CDCl3): δ 5.44–5.39 (1H, m), 4.93 (2H, s), 4.25–4.21 (1H, dd, J = 8 Hz), 2.42–2.26 (5H, m), 2.22–2.12 (3H, m), 1.65 (3H, s), 1.56 (1H, s); 13C-NMR (CDCl3) δ: 146.3, 134.2, 125.3, 106.5, 68.7, 38.3, 36.7, 28.2, 27.2, 26.5. CAS 7632-16-8.
(4): = +31.9 (CHCl3, c 0.03); IR (KBr) νmax: 3460, 2945, 2900, 1640, 1500, 1050, 880 cm–1; 1H-NMR (CDCl3): δ 5.45–5.33 (1H, m), 4.87 (2H, s), 4.22–4.19 (1H, dd, J = 8 Hz), 2.46–2.35 (5H, m), 2.17–2.08 (3H, m), 1.62 (3H, s), 1.58 (1H, s); 13C-NMR (CDCl3) δ: 147.8, 136.3, 123.1, 104.7, 69.5, 39.6, 36.5, 28.5, 27.2, 26.4. CAS 1197-06-4.
3.2.2. Epoxidation of (−)-cis-Carveol (3) and (+)-cis-Carveol (4)
A solution of
3 or
4 (6 g, 39.5 mmol) in CH
2Cl
2 (20 mL) was added to a solution of
m-chloroperbenzoic acid (9.51 g, 80%, 55.11 mmol) in CH
2Cl
2 (100 mL), and the resultant mixture was left at rest for 6 h. The filtered solution was washed with 10% aqueous NaHSO
3, (2 × 10 mL), with 10% aqueous NaHCO
3, (2 × 10 mL) and concentrated on a rotary evaporator. The product was purified by column chromatography on silica gel, using a mixture of hexane and ethyl acetate (9:1) as eluent. (−)-Carveol epoxide (
5) and (+)-carveol epoxide (
6) were obtained with 67% (26.42 mmol), and 65% (25.6 mmol) yields, respectively [
28,
29].
(5): = −17.6 (CHCl3, c 0.05); IR (KBr) νmax: 3485, 2990, 2350, 1600, 1375, 900 cm–1; 1H-NMR (CDCl3): δ 5.44–5.39 (1H, m), 4.93 (2H, s), 4.25–4.21 (1H, dd, J = 8 Hz), 2.42–2.26 (5H, m), 2.11–1.98 (3H, m), 1.65 (3H, s), 1.56 (1H, s); 13C-NMR (CDCl3): δ 146.3, 134.2, 125.3, 106.5, 68.7, 38.3, 36.7, 28.2, 27.2, 26.5. CAS 24120-79-4.
(6): = +16.8 (CHCl3, c 0.05); IR (KBr) νmax: 3500, 2980, 2350, 1600, 1350, 900 cm–1; 1H-NMR (CDCl3): δ 5.48–5.31 (1H, m), 4.87 (2H, s), 4.33–4.14 (1H, dd, J = 8 Hz), 2.53–2.35 (5H, m), 2.17–1.90 (3H, m), 2.15–2.01 (3H, m), 1.62 (1H, s), 1.58 (s); 13C-NMR (CDCl3) δ: 147.8, 136.3, 123.1, 104.7, 69.5, 39.6, 36.5, 28.5, 27.2, 26.4. CAS 39903-74-7.
3.2.3. Oxidation of (−)-Carveol Epoxide (5) and (+)-Carveol Epoxide (6)
A CrO
3-pyridine complex (7.5 g, 42 mmol) was added to a solution of compound
5 or
6 (2 g, 11.90 mmol) in pyridine (125 mL), and the resultant mixture was stirred for 30 h. The solvent was then concentrated on a rotary evaporator. The product was purified by column chromatography on silica gel, a mixture of hexane and ethyl acetate (9:1) being used as eluent. (−)-
trans-Carvone oxide (
9) and (+)-
trans-carvone oxide (
10) were obtained in 40% (5.35 mmol) and 45% (4.76 mmol) yield, respectively [
28].
(9): = −33.2 (CHCl3, c 0.01); IR (KBr) νmax: 3020, 2985, 1700, 880 cm–1; 1H-NMR (CDCl3z): δ 4.69–4.65 (2H, m), 3.38 (1H, d, J = 4.5), 2.74 (1H, dd, J = 15.6, J = 10.2), 2.48–2.60 (1H, m), 2.04–2.17 (1H, m), 2.02–2.16 (1H, m), 1.95 (1H, dd, J = 11.6, J = 15.2), 1.63 (3H, s), 1.33 (3H, s); 13C-NMR (CDCl3) δ: 206.5, 146.0, 110.3, 64.3, 58.3, 42.6, 41.4, 27.9, 18.8, 15.4. CAS 39903-98-5.
(10): = +32.1 (CHCl3, c 0.01); IR (KBr) νmax: 3025, 2975, 1720, 880 cm–1; 1H-NMR (CDCl3): δ 4.70–4.64 (2H, m), 3.36 (1H, d, J = 4.5), 2.75 (1H, dd, J = 15.8, J = 10.1), 2.49–2.61 (1H, m), 2.03–2.15 (1H, m), 2.02–2.14 (1H, m), 1.96 (1H, dd, J = 11.3, J = 15.4), 1.63 (3H, s), 1.35 (3H, s); 13C-NMR (CDCl3) δ: 206.7, 145.0, 110.6, 62.0, 59.4, 42.4, 41.5, 28.4, 20.2, 15.7. CAS 18383-49-8.
3.2.4. Epoxidation of (−)-Carvone (1) and (+)-Carvone (2)
A solution of
1 or
2 g (5 g; 33.33 mmol) was dissolved in MeOH (35 mL), 30% H
2O
2 (1021 mL; 9999 mmol) and 6N KOH (16.64 mL; 99.99 mmol), and the mixture was stirred for 4 h at 0 °C. The two-phase system was vigorously stirred at room temperature, and the phases were separated; the aqueous layer was extracted with Et
2O (3 × 20 mL). The organic phase was washed with water (3 × 20 mL), and dried with Na
2SO
3. The solvent was evaporated and the residue chromatographed on silica gel, using a mixture of hexane and ethyl acetate (9:1) as eluent. (+)-
cis-epoxycarvone (
7) and (−)-
cis-epoxycarvone (
8) were obtained in 76% (25.33 mmol) and 69% (23.0 mmol) yield, respectively [
29,
30].
(7): = +30.5 (CHCl3, c 0.03); IR (KBr) νmax: 2990, 2900, 1720, 1675, 880 cm–1; 1H-NMR (CDCl3): δ 4.69 (2H, m), 3.38 (1H, d, J = 4.5), 2.48–2.60 (1H, m), 2.04–2.17 (1H, m), 1.95 (1H, dd, J = 11.6), 1.70 (3H, s), 1.63 (3H, s); 13C-NMR (CDCl3) δ: 206.2, 146.4, 111.2, 63.2, 58.5, 41.8, 35.2, 28.8, 20.9, 15.7. CAS 36616-60-1.
(8): = −33.4 (CHCl3, c 0.03); IR (KBr) νmax: 2986, 2911, 1720, 1675, 890 cm–1; 1H-NMR (CDCl3): δ 4.71 (2H, m), 3.39 (1H, d, J = 4.5), 2.49–2.59 (1H, m), 2.03–2.17 (1H, m), 1.97 (1H, dd, J = 11.5), 1.70 (3H, s), 1.63 (3H, s); 13C-NMR (CDCl3) δ: 205.7, 146.8, 111.6, 63.2, 57.4, 41.4, 36.5, 28.8, 20.9, 15.5. CAS 39903-97-4.