The Journal of Organic Chemistry
Article
Using Olivetol as a Phenolic Compound. According to a general
procedure, the reaction of citral (240 mg, 1.57 mmol) with olivetol (200
mg, 1.61 mmol) in 6 mL of an aqueous emulsion of SDS under reflux for
(6aS,10aR)-6,6,9-Trimethyl-6a,7,8,10a-tetrahydro-6H-benzo[c]-
chromen-3-ol (4). A fraction enriched in compound 4 was subjected to
HPLC (normal phase, H/MTBE 85:15, t
= 26.5 min) to give pure 4 as
a colorless oil: H NMR (600 MHz, CDCl ) δ 7.08 (d, J = 8.3 Hz, 1H),
3
R
1
6
h provided after flash chromatography (H/MTBE, 5:1) mixture of
3
14 mg of compounds 15 and 16 (58%, 2.3:1 ratio).
6.37 (dd, J = 8.4, 2.6 Hz, 1H), 6.23 (d, J = 2.5 Hz, 1H) 5.88 (d, J = 5.3
Hz, 1H), 3.46 (s, 1H), 2.04−1.89 (m, 2H), 1.84 (dd, J = 13.0, 5.5 Hz,
1H), 1.69 (s, 3H), 1.60 (ddd, J = 12.8, 5.7, 2.8 Hz, 1H), 1.40 (s, 3H),
(
6aR,10aR)-6,6,9-Trimethyl-1-pentyl-6a,7,8,10a-tetrahydro-6H-
benzo[c]chromen-3-ol (15). A fraction enriched in compound 15 was
subjected to HPLC (normal phase, H/MTBE, 85:15, t = 10.7 min) to
give pure 15 as a colorless oil: H NMR (300 MHz, CDCl ) δ 6.33 (d,
1
3
1
1.26 (s, 3H), 1.25 (d, J = 5.7 Hz, 1H); C{ H} NMR (151 MHz,
CDCl ) δ 157.1, 155.6, 137.5, 131.8, 124.8, 120.1, 110.5, 106.3, 78.8,
42.1, 34.3, 33.0, 29.1, 28.2, 26.2, 22.3; HRMS (ESI-TOF) m/z [M +
R
12
1
3
3
J = 2.7 Hz, 1H), 6.16 (d, J = 2.6 Hz, 1H), 5.73−5.70 (m, 1H), 3.16 (d, J
+
=
12.7 Hz, 1H), 2.65 (t, J = 15.7 Hz, 2H), 2.23−2.17 (m, 2H), 1.99−
H] calcd for C16H O 245.1542, found 245.1533.
21 2
1.92 (m, 2H), 1.69 (s, 3H), 1.64−1.59 (m, 1H), 1.40 (s, 3H), 1.39−
1.34 (m, 6H), 1.06 (s, 3H), 0.93 (t, J = 11.9 Hz, 3H); C{ H} NMR
Reaction of Citral with Phenolic Compounds in Toluene and
Pyrrolidine: General Procedure. To a solution of citral and the
corresponding phenolic compound in dry toluene was added
pyrrolidine. The mixture was then heated at refluxing temperature
until the disappearance of the starting material. Then, the mixture was
diluted MTBE and washed with 2 N HCl. The organic layer was then
1
3
1
(
75 MHz, CDCl ) δ 154.8, 154.4, 143.4, 134.7, 126.8, 116.4, 108.7,
01.7, 76.9, 47.0, 34.7, 33.1, 31.8, 31.0, 30.9, 27.4, 25.1, 23.2, 22.5,
8.70, 14.05; HRMS (ESI-TOF) m/z [M + H] calcd for C H O
3
1
1
3
+
2
1
30
2
15.2324, found 315.2318.
washed with brine, dried with Na SO , and concentrated under a
(
1S,4R,4aR,5S,10bR)-4-((E)-2,6-Dimethylhepta-1,5-dien-1-yl)-
2
4
2
,2,5-trimethyl-8-pentyl-1,4a,5,10b-tetrahydro-2H,4H-1,5-
vacuum. The residue was purified by column chromatography.
Using Resorcinol as a Phenolic Compound. According to the
general procedure, toluene (11 mL), pyrrolidine (213 mg, 3 mmol),
citral (230 mg, 1.51 mmol), and resorcinol (300 mg, 2.27 mmol) were
heated. After 3 h, 100 mL of MTBE were added, and the resulting
solution was washed with a solution of 2 N HCl (2 × 50 mL) and brine
ethanopyrano[3,4-c]chromen-10-ol (16). A fraction enriched in
compound 16 was subjected to HPLC (normal phase, H/MTBE,
3
CDCl ) δ 6.18 (d, J = 0.8 Hz, 1H), 6.02 (d, J = 1.2 Hz, 1H), 5.23 (d, J =
1
:1, t = 8.5 min) to give pure 16 as a colorless oil: H NMR (300 MHz,
R
3
8
.0 Hz, 1H), 5.02 (s, 1H), 4.83 (d, J = 8.4 Hz, 1H), 4.39 (s, 1H), 2.38 (t,
J = 7.9 Hz, 3H), 1.97 (m, 2H), 2.21 (m, 2H), 1.97 (s, 1H), 1.73 (s, 3H),
.65 (s, 3H), 1.58 (s, 3H), 1.51 (s, 3H), 1.47 (s, 3H), 1.43 (s, 3H), 1.31
(3 × 50 mL). The organic layer was dried with Na SO and
2 4
1
concentrated under a vacuum. Purification with silica gel chromatog-
s, 3H), 1.12 (m, 4H), 1.02 (s, 2H), 0.81 (t, J = 6.9 Hz, 3H); 13C{ H}
1
11
(
raphy yielded 6% of 5 as a colorless oil (H/MTBE, 4:1) (44 mg, 0.18
11
NMR (75 MHz, CDCl ) δ 156.7, 151.5, 142.5, 135.5, 131.9, 127.1,
mmol) and 8% of 6 as a colorless oil (H/MTBE, 4:1) (33 mg, 0.13
3
1
3
23.9, 107.6, 105.8, 78.5, 77.2, 76.9, 76.7, 75.3, 70.8, 41.5, 39.0, 35.7,
mmol).
(2-Methyl-2-(4-methylpent-3-en-1-yl)-2H-chromen-5-ol (5): 1
H
5.6, 32.5, 31.5, 30.7, 28.5, 26.2, 25.6, 23.9, 23.1, 22.5, 20.6, 17.6, 14.0;
+
HRMS (ESI-TOF) m/z [M + H] calcd for C H O 467.3525, found
NMR (500 MHz, CDCl ) δ 6.95 (t, J = 8.1 Hz, 1H), 6.67 (d, J =
3
3
1
47
3
4
67.3522.
10.5 Hz, 1H), 6.44−6.40 (td, 1H), 6.30 (dd, J = 8.1, 0.9 Hz, 1H), 5.58
(d, J = 10.0 Hz, 1H), 5.12 (tt, J = 7.1, 1.4 Hz, 1H), 2.18−2.08 (m, 2H),
1.80−1.69 (m, 2H), 1.69−1.67 (m, 3H), 1.60 (d, J = 1.3 Hz, 3H), 1.41
Reaction of Citral with Phenolic Compounds in Water and
4
NH Cl: General Procedure. To a round-bottom flask containing
citral was added an aqueous solution of NH Cl. The mixture was then
1
3
1
(s, 3H); C{ H} NMR (126 MHz, CDCl ) δ 154.3, 151.2, 131.71,
4
3
heated at refluxing temperature (oil bath) until the disappearance of the
starting material. Then, brine was added, and the aqueous phase was
128.9, 128.3, 124.1, 116.7, 109.4, 109.2, 107.4, 78.2, 41.1, 26.3, 25.7,
22.7, 17.6.
extracted with MTBE (×3). The organic layer was dried with Na SO4
2-Methyl-2-(4-methylpent-3-en-1-yl)-2H-chromen-7-ol (6): 1
H
2
and concentrated under a vacuum. The residue was purified by column
chromatography
NMR (500 MHz, CDCl ) δ 6.84 (d, J = 7.9 Hz, 1H), 6.35−6.28 (m,
3
3H), 5.44 (d, J = 9.8 Hz, 1H), 5.12 (tp, J = 7.2, 1.5 Hz, 1H), 2.18−2.06
(m, 2H), 1.75 (ddd, J = 13.9, 10.6, 6.1 Hz, 1H), 1.68 (bs, 3H), 1.67−
Using Orcinol as a Phenolic Compound. According to a general
procedure, the reaction of citral (150 mg, 0.98 mmol) with orcinol (122
1
3
1
1.61 (m, 1H), 1.59 (bs, 3H), 1.40 (s, 3H); C{ H} NMR (126 MHz,
mg, 0.98 mmol) in 22 mL of an aqueous solution of NH Cl (11 mg,
CDCl ) δ 156.43, 154.65, 131.71, 127.17, 126.82, 124.13, 122.37,
3
4
0
.20 mmol) under reflux for 24 h provided after flash chromatography
114.75, 107.34, 103.49, 78.78, 41.37, 26.62, 25.68, 22.73, 17.63.
Using Orcinol as a Phenolic Compound. According to the general
procedure, toluene (4 mL), pyrrolidine (46 mg, 0.66 mmol), citral (82
mg, 0.53 mmol), and orcinol (96 mg, 0.78 mmol) were heated. After 13
h, 50 mL of MTBE was added, and the resulting solution was washed
with a solution of HCl (2 N) (2 × 25 mL) and brine (3 × 25 mL). The
organic layer was dried with Na SO and concentrated under a vacuum.
(
H/MTBE, 4:1) 54% of compound 9 as a colorless oil (139 mg, 0.52
12
mmol) and 14% (35 mg, 0.14 mol) of compound 10 as a colorless oil.
1′R,2′R)-5′,6-Dimethyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahy-
dro-[1,1′-biphenyl]-2,4-diol (10): IR (neat) 3414, 2966, 2922, 1620,
594, 1464, 1376, 1328, 1264, 1149, 1136, 1055, 989, 890, 840, 738
(
1
−
1 1
cm ; H NMR (600 MHz, CDCl ) δ 6.22 (bs, 1H), 6.14 (bs, 1H), 5.55
3
2
4
13
(
bs, 1H), 4.66 (bs, 1H), 4.47 (bs, 1H), 3.56 (d, J = 8.7 Hz, 1H), 2.49−
Purification with silica gel chromatography yielded 68% of 11 as a
colorless oil (H/MTBE, 5:1) (93 mg, 0.36 mmol).
2
1
1
3
.43 (m, 1H), 2.27−2.07 (m, 2H), 2.16 (s, 3H), 1.87−1.72 (m, 2H),
1
3
1
.80 (s, 3H), 1.58 (s, 3H); C{ H} NMR (151 MHz, CDCl ) δ 156.4,
54.4, 147.6, 139.8, 139.0, 124.5, 120.5, 111.5, 109.4, 102.1, 45.1, 40.2,
0.2, 28.0, 23.6, 21.1, 20.9; HRMS (ESI-TOF) m/z [M + H] calcd for
2,7-Dimethyl-2-(4-methylpent-3-en-1-yl)-2H-chromen-5-ol (11):
3
1
H NMR (300 MHz, CDCl ) δ 6.64 (dd, J = 10.0, 0.8 Hz, 1H), 6.30−
3
+
6.25 (m, 1H), 6.17−6.13 (m, 1H), 5.52 (d, J = 10.0 Hz, 1H), 5.13 (ddq,
J = 8.9, 6.0, 1.6 Hz, 1H), 2.24 (s, 3H), 2.19−2.09 (m, 2H), 1.79−1.70
(m, 2H), 1.69 (d, J = 1.4 Hz, 3H), 1.61 (d, J = 1.3 Hz, 3H), 1.40 (s, 3H);
C H O 259.1698, found 259.1690.
17
23
2
Using Olivetol as a Phenolic Compound. According to the general
procedure, the reaction of citral (150 mg, 0.98 mmol) with orcinol (177
mg, 0.98 mmol) in 22 mL of an aqueous solution of NH Cl (11 mg,
1
3
1
C{ H} NMR (75 MHz, CDCl ) δ 154.2, 151.43, 139.8, 131.9, 127.4,
3
4
124.4, 116.9, 110.1, 108.5, 106.9, 78.4, 41.3, 26.6, 25.9, 23.0, 21.8, 17.9.
Reaction of Citral with Phenolic Compounds in the Presence
of Lewis Acids: General Procedure. To a solution of citral and the
corresponding phenolic compound in dry toluene was added the
corresponding Lewis acid. The mixture was then stirred at room
temperature until the disappearance of the starting material. Then, the
mixture was concentrated under a vacuum, and the residue was purified
by column chromatography.
0
.20 mmol) under reflux for 24 h provided after flash chromatography
(H/MTBE, 4:1) 75% of compound 13 (230 mg, 0.73 mmol).
Reaction of Citral with Resorcinol in Water and DBSA. To a
solution of DBSA (0.45 mmol, 148 mg) in 15 mL of water were added
resorcinol (100 mg, 0.9 mmol) and then citral (207 mg, 1.5 mmol). The
mixture was then heated at refluxing temperature (oil bath) for 1 h.
Then, brine was added, and the aqueous later was extracted with MTBE
(
3 × 50 mL). The combined organic layers were washed with brine (3 ×
Using Resorcinol as a Phenolic Compound. According to the
general procedure, dichloromethane (10 mL), citral (303 mg, 1.9
mmol), resorcinol (1) (200 mg, 1.8 mmol), and Lewis acid (0.18 mmol,
0.1 equiv) were stirred. After 0.5−14.5 h, the mixture was concentrated
1
00 mL), dried with Na SO , and concentrated under a vacuum. The
2
4
residue was flash chromatographed (H/MTBE, 4:1) to afford 68 mg of
a mixture of 3 and 4 (31%, 1.2:1 ratio).
3
352
J. Org. Chem. 2021, 86, 3344−3355