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concentrated under reduced pressure. The desired product 9 (cmꢀ1) 3428, 3328, 2927, 2867, 1629, 1575, 1498, 1456, 1383,
(0.301 g, 1.05 mmol, 96%, 51% ee) was obtained as a white 1362, 1085, 1036, 905, 883, 822.
solid, which was used for next step without further purication.
1
Mp: 105.0–108.0 C. H NMR (300 MHz, CDCl3): d (ppm) 7.80– Dehydroabietyl cyanide (12)26
ꢁ
7.68 (m, 3H), 7.50–7.38 (m, 1H), 7.22–7.08 (m, 2H), 4.66–4.42
To a stirred solution of 11 (5.49 g, 18.3 mmol) in dry CH2Cl2 (100
(br, 2H), 4.04–3.84 (m, 4H), 2.19 (s, 3H), 1.67 (d, J ¼ 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): d (ppm) 168.8, 160.3, 157.9, 135.4,
133.9, 129.2, 128.9, 127.6, 126.2, 125.5, 119.3, 105.7, 55.4, 41.3,
19.9, 17.7. IR (KBr): n (cmꢀ1) 3449, 3332, 3196, 3060, 2962, 2936,
2841, 1744, 1627, 1505, 1486, 1464, 1439, 1418, 1392, 1371,
1266, 1227, 1173, 1119, 1027, 1010, 957, 927, 885, 855, 814.
HPLC analysis (Daicel Chiralcel OD-3, hexane/2-propanol ¼
80 : 20, 1.0 mL minꢀ1, 254 nm UV detector; tr(S) ¼ 13.8 min,
tr(R) ¼ 30.7 min).
mL), PPh3 (7.20 g, 27.4 mmol), dry triethylamine (2.78 g, 27.4
mmol) and dry CCl4 (4.23 g, 27.5 mmol) were added under
a nitrogen atmosphere. The solution was reuxed for 17 h. Aer
the reaction was quenched with H2O, the organic layer was
separated, washed with 1 N HCl aq., dried over anhydrous
Na2SO4, ltered and concentrated under reduced pressure. The
crude product (14.8 g) was puried by silica gel column chro-
matography (eluent: hexane/CHCl3 ¼ 1/1, v/v). The desired
product 12 (4.77 g, 16.9 mmol, 93%) was obtained as a white
solid. Mp: 77.0–80.0 ꢁC. [a]D26 ¼ +37.0ꢁ (c 1.00, CHCl3). 1H NMR
(300 MHz, CDCl3): d (ppm) 7.20–7.10 (m, 1H), 7.06–6.92 (m, 1H),
6.92–6.86 (m, 1H), 3.10–2.92 (m, 2H), 2.92–2.70 (m, 1H), 2.40–
2.24 (m, 1H), 2.14–1.66 (m, 8H), 1.42 (s, 3H), 1.22 (d, J ¼ 6.9 Hz,
6H), 1.18 (s, 3H). 13C NMR (100 MHz, CDCl3): d (ppm) 146.2,
145.4, 134.2, 127.0, 126.6, 124.2, 124.0, 46.8, 37.5, 37.4, 37.3,
2-(6-Methoxy-2-naphthyl)propionamidine (2b)
A suspension of 9 (0.720 g, 2.51 mmol) and 10% Pd–C (0.173 g)
in EtOH (30 mL) was stirred under a hydrogen atmosphere at
room temperature for 2 h. The solid was ltered off and the
ltrate was concentrated under reduced pressure. The residue
(0.752 g) was recrystallized from MeOH (8.5 mL) to give the
acetate salt of the product as a solid. The separated ltrate was
concentrated under reduced pressure and the residue was
recrystallized from EtOH/H2O (4 mL/0.5 mL). The combined
solid was dissolved in CHCl3 (30 mL) and 1 N NaOH aq. (20 mL)
was added. The aqueous layer was separated and extracted with
CHCl3 (15 mL ꢂ 5). The combined organic layer was washed
with sat. NaCl aq., dried over anhydrous Na2SO4, ltered and
concentrated under reduced pressure. The desired product 2b
(0.597 g, 2.07 mmol, 83%, racemic) was obtained as a white
37.2, 33.5, 29.8, 25.2, 23.9, 21.7, 18.9, 17.7. IR (KBr): n (cmꢀ1
)
3010, 2930, 2930, 2863, 2225, 1612, 1496, 1458, 1419, 1383, 889,
819. MS (MALDI-TOF) m/z calcd for C20H27N + Na+: 304.204 [M +
Na]+; found: 304.245.
N-Hydroxy-dehydroabietyl amidine (13)
To a stirred solution of 12 (4.76 g, 16.9 mmol) in dry EtOH (35
mL), H2NOH$HCl (5.89 g, 84.8 mmol) and dry triethylamine
(8.58 g, 84.8 mmol) were added, and then the solution was
reuxed under a nitrogen atmosphere for 28 h. Aer cooling to
room temperature, the solution was concentrated under
reduced pressure. The residue was dissolved in AcOEt (100 mL)
and washed with H2O and sat. NaCl aq. The organic layer was
dried over anhydrous Na2SO4, ltered and concentrated under
reduced pressure. The crude product (5.76 g) was puried by
silica gel column chromatography (eluent: hexane/AcOEt ¼ 2/1,
v/v). The desired product 13 (1.66 g, 5.29 mmol, 31%) was ob-
tained as a white solid. Mp: 89.7–91.7 ꢁC. [a]D24 ¼ +86.2ꢁ (c 1.00,
CHCl3). 1H NMR (300 MHz, CDCl3): d (ppm) 7.22–7.12 (m, 1H),
7.04–6.94 (m, 1H), 6.94–6.84 (m, 1H), 4.80–4.48 (br, 2H), 2.98–
2.74 (m, 3H), 2.45–2.28 (m, 1H), 2.00–1.56 (m, 8H), 1.34–1.18
(m, 12H). 13C NMR (100 MHz, CDCl3): d (ppm) 160.0, 147.2,
145.9, 134.8, 127.0, 124.0, 123.9, 46.3, 42.8, 38.3, 37.5, 37.4, 33.5,
30.0, 25.5, 24.0, 20.1, 18.7, 16.0. IR (KBr): n (cmꢀ1) 3500, 3399,
3255, 2930, 1651, 1575, 1497, 1457, 1382, 1362, 1230, 1197,
1173, 1140, 1074, 923, 822. MS (MALDI-TOF) m/z calcd for
26
1
ꢁ
solid. Mp: 125.0–129.0 C. [a]D ¼ 0ꢁ (c 1.00, CHCl3). H NMR
(300 MHz, CDCl3): d (ppm) 7.80–7.62 (m, 3H), 7.40–7.30 (m, 1H),
7.22–7.04 (m, 2H), 3.92 (s, 3H), 3.73 (q, J ¼ 7.2 Hz, 1H), 1.58 (d, J
¼ 7.2 Hz, 3H). IR (KBr): n (cmꢀ1) 3321, 3163, 2966, 1684, 1635,
1606, 1505, 1485, 1455, 1436, 1392, 1264, 1216, 1163, 1030, 927,
891, 853.
Dehydroabietyl amide (11)25
To a stirred solution of dehydroabietic acid (10) (2.01 g, 6.09
mmol) in dry CH2Cl2 (3 mL), DMF (3 drops) and oxalyl chloride
(1.5 mL) were added under a nitrogen atmosphere at 0 ꢁC, and
the solution was reuxed for 2 h. Aer the volatile components
were distilled off, dry toluene (10 mL) and 28% NH3 aq. (3 mL)
were added at 0 ꢁC. The resulting suspension was stirred at
room temperature for 2 h, and then was added to AcOEt (100
mL) and H2O (50 mL). The organic layer was separated and
washed with sat. NaHCO3 aq. and sat. NaCl aq. The organic
phase was dried over anhydrous Na2SO4, ltered and concen-
trated under reduced pressure. The desired product 11 (1.95 g,
C
20H30N2O + H+: 315.244 [M + H]+; found: 315.242.
N-Acetoxy-dehydroabietyl amidine (14)
6.50 mmol, 97%) was obtained as a pale yellow solid, which was To a stirred solution of 13 (1.64 g, 5.21 mmol) in THF (44 mL),
used for next step without further purication. Mp: 153.0– pyridine (0.503 g, 6.36 mmol) and acetic anhydride (0.638 g,
156.0 ꢁC. [a]D25 ¼ +41.1ꢁ (c 1.00, CHCl3). 1H NMR (300 MHz, 6.25 mmol) were added at 0 ꢁC, and then the solution was
CDCl3): d (ppm) 7.22–7.12 (m, 1H), 7.04–6.96 (m, 1H), 6.90–6.82 stirred at room temperature for 1 h. Aer the solvent was
(m, 1H), 5.90–5.60 (br, 1H), 5.50–5.20 (br, 1H), 2.96–2.85 (m, distilled off, the residue was dissolved in CHCl3 (50 mL), and
2H), 2.85–2.73 (m, 1H), 2.39–2.25 (m, 1H), 2.16–2.04 (m, 1H), washed with 1 N HCl aq., sat. NaHCO3 aq. and sat. NaCl aq. The
1.90–1.40 (m, 7H), 1.29 (s, 3H), 1.26–1.14 (m, 9H). IR (KBr): n organic layer was dried over anhydrous Na2SO4, ltered and
© 2021 The Author(s). Published by the Royal Society of Chemistry
RSC Adv., 2021, 11, 18162–18170 | 18167