Synthesis of Hotrienol
J. Agric. Food Chem., Vol. 51, No. 14, 2003 4037
Linalyl Isobutyrate (2c). The product was recovered as an oil (46
g, 76%). The purity was 99% by GC. Bp. 68-69 °C/0.3 Torr; IR-
(diastereomer mixture) 1.15 (d, J ) 7 Hz, 3H), 1.54 and 1.79 (each s,
3H), 1.67-2.02 (m, 4H), 1.79 (s, 3H), 2.47-2.53 (m, 1H), 4.32-4.35
(m, 1H), 4.91 and 5.01 (each brs, 1H), 5.12-5.19 (m, 2H), 5.87-5.95
(m, 1H); 13C NMR (diastereomer mixture) 16.77 (CH3), 16.78 (CH3),
18.96 (CH3 × 2), 23.75 (CH3), 23.90 (CH3), 30.69 (CH2), 30.72 (CH2),
34.72 (CH), 34.75 (CH), 36.98 (CH2), 66.48 (CH), 66.55 (CH), 81.62
(C), 81.75 (C), 113.32 (CH2), 113.37 (CH2), 114.39 (CH2), 114.45
(CH2), 141.37 (CH), 141.52 (CH), 143.91 (C), 143.96 (C), 175.73 (Cd
O), 175.74(CdO); MS m/z 258 (1), (M+), 223 (11), 215 (1), 207 (2),
197 (1), 188 (2), 179 (2), 171 (2), 155 (4), 143 (15), 135 (71), 127 (3),
119 (14), 107 (43), 93 (46), 81 (58), 71 (100), 55 (28), 43 (69), 27 (8).
6-Chloro-3,7-dimethyl-1,7-octadien-3-yl Benzoate (3d). The prod-
uct was recovered as an oil (8.7 g, 80%) from linalyl benzoate 2d (9.5
g, 37 mmol). The purity was 92% by GC. Bp. 135-138 °C/0.6 Torr;
1
(neat) 3087, 2973, 2932, 1733, 1644, 1468 cm-1; H NMR 1.15 (t, J
) 7 Hz, 3H), 1.53, 1.59, and 1.67 (each s, 3H), 1.72-1.78 (m, 1H),
1.85-1.95 (m, 1H), 1.96-2.00 (m, 2H), 2.46-2.52 (m, 1H), 5.08-
5.17 (m, 3H), 5.95 (dd, J ) 11, 17.5 Hz, 1H); 13C NMR 17.48 (CH3),
18.99 (CH3 × 2), 22.27 (CH2), 23.63 (CH3), 25.60 (CH3), 34.81 (CH),
39.79 (CH2) 82.27 (C), 112.85 (CH2), 123.83 (CH), 131.69 (C), 141.98
(CH), 175.82 (CdO); MS m/z 224 (2) (M+), 209 (1), 197(1), 181 (1),
154 (2), 136 (8), 121 (7), 107 (7), 93 (100), 80 (27), 69 (26), 57 (8),
43 (24), 41 (20), 27 (3).
Linalyl Benzoate (2d). The product was recovered as an oil (43.2
g, 62%). The purity was 95% by GC. Bp. 110-112 °C/0.3 Torr; IR-
(neat) 3085, 2970, 2727, 1718, 1643, 1601, 1451 cm-1; 1H NMR 1.59,
1.65, and 1.69 (each s, 3H), 1.89-1.94 (m, 1H), 1.97-2.11 (m, 3H),
5.12-5.28 (m, 3H), 6.09 (dd, J ) 11, 17.5 Hz, 1H), 7.39-7.50 (m,
2H), 7.51-7.54 (m, 1H), 8.01-8.02 (m, 2H); 13C NMR 17.52 (CH3),
22.42 (CH2), 23.71 (CH3), 25.57 (CH3), 40.01 (CH2), 83.46 (C), 113.22
(CH2), 123.78 (CH), 128.18 (CH), 129.40 (CH × 2), 131.59 (C), 131.69
(C), 132.50 (CH × 2), 141.81 (CH), 165.16 (CdO); MS m/z 258 (2)
(M+), 243 (1), 229 (1), 215 (1), 207 (1), 189 (2), 175 (2), 153 (2), 136
(9), 121 (21), 105 (100), 93 (97), 77 (29), 69 (15), 51 (9), 41 (16), 27
(3).
General Procedure for the Preparation of 6-Chloro-3,7-dimethyl-
1,7-octadien-3-yl Acylate (3) by Ene-Type Chlorination. To a 200-
mL, four-necked, round-bottomed flask equipped with a mechanical
stirrer, a reflux condenser, a thermometer and a pressure-equalizing
dropping funnel were added linalyl acylate (50 mmol) in CH2Cl2 (50
mL), 60% calcium hypochlorite (5.8 g, 25 mmol), and boric acid (6.2
g, 100 mmol). To the mixture, stirred at 5 °C, water (10 mL) was added
dropwise over 3.5 h. The reaction mixture was stirred at the same
temperature for 1 h, and then sodium sulfide (2.5 g, 19.9 mol) was
added. The inorganic salt was filtered off, and the organic layer was
separated and washed twice with 10% NaCl solutions. The solvent was
removed under vacuum, and the product was distilled under reduced
pressure to give 3.
6-Chloro-3,7-dimethyl-1,7-octadien-3-yl Acetate (3a). The product
was recovered as an oil (10.1 g, 88%) from linalyl acetate 2a (9.8 g,
50 mmol). The purity was 94% by GC. From 1500 g of 2a, 1545 g
(88%) of 3a was obtained, by a scale-up proceduce. The purity was
92% by GC. Bp. 69-72 °C/0.3 Torr; IR(neat) 3084, 2977, 1738, 1646,
1450, 1371 cm-1; 1H NMR (diastereomer mixture) 1.53 and 1.55 (each
s, 3H), 1.63-1.70 (m, 1H), 1.77-1.87 (m, 2H), 1.78 (s, 3H), 1.90-
1.97 (m, 1H), 1.99 (s, 3H), 4.31 (t, J ) 7.4 Hz, 1H), 4.88 and 4.99
(each brs, 1H), 5.10-5.16 (m, 2H), 5.91 (dt, J ) 11.3, 17.5 Hz, 1H);
13C NMR (diastereomer mixture) 16.75 (CH3), 16.77 (CH3), 20.04
(CH3), 22.04 (CH3), 23.62 (CH3), 23.74 (CH3), 30.69 (CH2), 30.72
(CH2), 37.00 (CH2), 37.02 (CH2), 66.47 (CH), 66.54 (CH), 82.15 (C),
82.27 (C), 113.47 (CH2), 113.52 (CH2), 114.41 (CH2), 114.46 (CH2),
141.16 (CH), 141.30 (CH), 143.88 (C), 143.92 (C), 169.73 (CdO);
MS m/z 230 (1) (M+), 195 (10), 171 (2), 153 (14), 135 (22), 121 (31),
107 (29), 93 (100), 80 (61), 67 (49), 55 (24), 43 (84).
1
IR(neat) 3087, 2975, 1717, 1646 1601, 1584, 1451 cm-1; H NMR
(diastereomer mixture); 1.69, 1.70, and 1.79 (each s, 3H), 1.81-2.16
(m, 4H), 4.36-4.40 (m, 1H), 4.91, and 5.03 (each brs, 1H), 5.19-
5.23 (m, 1H), 5.25-5.31 (m, 1H), 6.01-6.10 (m, 1H), 7.09-7.46 (m,
2H), 7.52-7.56 (m, 1H), 7.99-8.01 (m, 2H); 13C NMR (diastereomer
mixture) 16.85 (CH3), 23.87 (CH3), 23.94 (CH3), 30.79 (CH2), 30.81
(CH2), 37.20 (CH2), 37.23 (CH2), 66.48 (CH), 66.56 (CH), 82.84 (C),
82.97 (C), 113.73 (CH2), 113.77 (CH2), 114.48 (CH2), 114.53 (CH2),
128.21 (CH × 2), 128.26 (CH × 2), 129.38 (CH × 2), 129.51 (CH ×
2), 132.70 (CH), 141.24 (CH), 141.33 (CH), 143.86 (C), 143.92 (C),
165.09 (CdO); MS m/z 257 (13), (M+-35), 207 (2), 188 (2), 170 (2),
155 (2), 135 (37), 119 (9), 105 (100), 93 (20), 77 (45), 68 (20), 53
(13), 41 (11).
General Procedure for the Preparation of 3,7-Dimethyl-1,5(E),7-
octatrien-3-yl Acylate (4) by Dehydrochlorination. To a 200-mL,
four-necked, round-bottomed flask equipped with a mechanical stirrer,
a reflux condenser and a thermometer were added 3 (8.6 g, 35 mmol)
in DMF (70 mL), lithium carbonate (6.46 g, 87.5 mmol), and lithium
bromide (11.7 g, 52.5 mmol). The reaction mixture was stirred at 130
°C for 2 h. The conversion and selectivity were 98% and 78%,
respectively. The vessel was cooled to 70 °C and then DMF was
recovered under vacuum. Toluene (100 mL) and water (100 mL) were
added to the residue. The organic layer was washed with water (100
mL) and then 10% NaCl solution (100 mL). The solvent was recovered
under vacuum, and the product was distilled under reduced pressure
to give 4.
3,7-Dimethyl-1,5(E),7-octatrien-3-yl Acetate (4a). The product was
recovered as an oil (4.9 g, 73%) from 3a (8.1 g). The purity was 94%
by GC. 725 g (73%) of 4a was obtained from 1200 g of 3a by a scale-
up proceduce. The purity were 93% by GC. Bp. 48 °C/0.4 Torr. IR
(neat) 3084, 2977, 2940, 1738, 1645, 1609, 1437 cm-1; 1H NMR 1.44
and 1.76 (each s, 3H) 1.92 (s, 3H), 2.51-2.60 (m, 2H), 4.89 (brs, 2H),
5.06 (d, J ) 11 Hz, 1H), 5.09 (d, J ) 16.2 Hz, 1H), 5.49 (dt, J ) 7.4,
15.6 Hz, 1H), 5.94 (dd, J ) 11, 17.5 Hz, 1H), 6.09 (d, J ) 15.6 Hz,
1H); 13C NMR 18.54 (CH3), 22.04 (CH3), 23.55 (CH3), 42.72 (CH2),
82.42 (C), 113.43 (CH2), 115.26 (CH2), 124.19 (CH), 136.43 (CH),
141.47 (CH), 141.73 (C), 169.83 (CdO); MS m/z 194 (1) (M+), 151
(1), 134 (51), 119 (76), 113 (7), 105 (17), 91 (45), 71 (100), 55 (94),
43 (94).
6-Chloro-3,7-dimethyl-1,7-octadien-3-yl Propionate (3b). The
product was recovered as an oil (10.6 g, 87%) from linalyl propionate
2b (10 g, 50 mmol). The purity was 94% by GC. Bp. 85-87 °C/1
3,7-Dimethyl-1,5(E),7-octatrien-3-yl Propionate (4b). The product
was recovered as an oil (4.8 g, 71%) from 3b (8.0 g, 32.7 mmol). The
purity was 94% by GC. Bp. 52-54 °C/0.3 Torr. IR (neat) 3084, 2979,
1
Torr; IR(neat) 3085, 2979, 2943, 1738, 1645, 1460 cm-1; H NMR
1
(diastereomer mixture) 1.11 (t, J ) 7.5 Hz, 3H), 1.65 and 1.66 (each
s, 3H), 1.68-2.00 (m, 4H), 1.79 (s, 3H), 2.29 (q, J ) 8.5, 15.1 Hz,
2H), 4.32-4.35 (m, 1H), 4.91 and 5.01 (each brs, 1H), 5.12-5.19 (m,
2H), 5.89-5.97 (m, 1H); 13C NMR (diastereomer mixture) 9.15 (CH3),
16.79 (CH3), 16.80 (CH3), 23.72 (CH3), 23.85 (CH3), 28.49 (CH2), 28.51
(CH2), 30.73 (CH2), 30.76 (CH2), 37.06 (CH2), 37.07 (CH2), 66.53 (CH),
66.60 (CH), 81.90 (C), 82.03 (C), 113.44 (CH2), 113.49 (CH2), 114.45
(CH2), 114.50 (CH2), 141.32 (CH), 141.48 (CH), 143.92 (C), 143.97
(C), 173.18 (CdO); MS m/z 215(1) (M+ - 29), 209(6), 170 (2), 155
(4), 141 (6), 135 (42), 127 (21), 119 (13), 107 (30), 93 (32), 81 (47),
68 (43), 57 (100), 41 (17), 29 (17).
2941, 1737, 1645, 1609, 1460 cm-1; H NMR 1.09 (t, J ) 7.6 Hz,
3H), 1.52 and 1.82 (each s, 3H), 2.26 (q, J ) 7.6, 15.6 Hz, 2H), 2.59-
2.68 (m, 2H), 4.89 (brs, 2H), 5.14 (dd, J ) 1.1, 10 Hz, 1H), 5.17 (dd,
J ) 1.1, 20.4 Hz, 1H), 5.57 (dt, J ) 7.6, 15.6 Hz, 1H), 6.01 (dd, J )
10.9, 17.5 Hz, 1H), 6.17 (d, J ) 15.6 Hz, 1H); 13C NMR 9.15 (CH3),
18.54 (CH3), 23.67 (CH3), 28.55 (CH2), 42.68 (CH2), 82.10 (C), 113.34
(CH2), 115.22 (CH2), 124.25 (CH), 136.40 (CH), 141.63 (CH), 141.74
(C), 173.21 (CdO). MS m/z 208 (1), (M+), 179 (1), 165 (1), 151 (1),
140 (6), 134 (53), 127 (15), 119 (74), 105 (17), 91 (32), 79 (23), 71
(17), 57 (100), 41 (4), 29 (13).
3,7-Dimethyl-1,5(E),7-octatrien-3-yl 2-Methylpropionate (4c). The
product was recovered as an oil (5.4 g, 69%) from 3c (9.0 g). The
purity was 93% by GC. Bp. 63-65 °C/0.2 Torr. IR (neat) 3084, 2974,
6-Chloro-3,7-dimethyl-1,7-octadien-3-yl 2-Methylpropionate (3c).
The product was recovered as an oil (11 g, 85%) from linalyl isobutyrate
2c (11.2 g, 50 mmol). The purity was 95% by GC. Bp. 93-96 °C/0.6
1
2937, 1735, 1646, 1610, 1469 cm-1; H NMR 1.12 (d, J ) 7.4 Hz,
1
Torr; IR(neat) 3083, 2975, 2938, 1733, 1640, 1468 cm-1; H NMR
3H), 1.52 and 1.82 (each s, 3H), 2.44-2.50 (m, 1H), 2.65 (d, J ) 7.4