from 11,12-didehydroretinol via the corresponding bromide,
provided 11,12,11Ј-12Ј-tetrahydro-β-carotene32 6. Catalytic
semihydrogenation of 3 and 6 gave 433 and 7,32 respectively.
Detailed preparative procedures will be described below.
mmol) in 50 ml of dichloromethane under argon and Ϫ25 ЊC
was slowly added 0.94 ml of a 30% solution of sodium meth-
oxide in methanol. After 30 min stirring, the solvents were
evaporated and the residue partitioned between a 1:1 mixture
of hexane–ethyl acetate 4:1 and methanol–water 4:1. The
hexane–ethyl acetate phase was separated, dried over sodium
sulfate and concentrated under vacuum. The oily residue (2.6 g)
was purified by column chromatography over silica gel to
yield 1.34 g of crude 11,12,11Ј,12Ј-tetradehydro-β-carotene 6.
Recrystallization from hexane gave 278 mg (10.4%) of 6 as an
orange solid, mp 122–125 ЊC (lit.,32 98–100 ЊC) (Calc. for
C40H52: C, 90.16; H, 9.84%. Found: C, 89.75; H, 9.81%); MS
m/z 532 (Mϩ, 80%), 517 (22%), 69 (100%); λ/nm 271 (21.7), 417
(93.3); δH 6.50–6.53 (4H, m, 14,14Ј,15,15ЈH), 6.26 (2H, d, J 16,
7,7ЈH), 6.13 (2H, d, J 16, 8,8ЈH), 5.58 (2H, s, 10,10ЈH), 2.07
(6H, s, 9,9ЈMe), 2.01 (4H, t, J 6, 4,4ЈH), 1.99 (6H, s, 13,13ЈMe),
1.7 (6H, s, 5,5ЈMe), 1.61 (4H, m, 3,3ЈH), 1.46 (4H, m, 2,2ЈH),
1.02 (12H, s, 1,1ЈMe).
11,11Ј-di-cis-â-Carotene 7. To a solution of 11,12,11Ј,12Ј-
tetradehydro-β-carotene 6 (1 g, 1.88 mmol) in 50 ml of dry
ethyl acetate were added 0.78 g of Lindlar catalyst and 80 µl of
quinoline. The reaction mixture was hydrogenated for 1 h at
room temp. and 1 atm, then filtered over aluminium oxide and
the solvent evaporated under vacuum at 20 ЊC. The oil obtained
was dissolved in 10 ml dichloromethane and methanol was
added until precipitation of a dark red solid which was removed
by filtration. Two crystallizations from dichloromethane–
methanol 1:1 gave 442 mg of crude material containing 3.5%
all-trans-β-carotene, 6% unknown isomer and 86% 11,11Ј-di-
cis-β-carotene32 7.
Intermediates 3, 5 and 6 were characterized at Hoffmann-La
Roche, Basel. Mass spectra were obtained on an MS 9 (AEI, GB-
Manchester) spectrometer at 70 eV. Data are given as m/z (%).
UV spectra (in hexane containing 2% chloroform) were
recorded on a Uvikon 810 instrument; each result is shown as
λmax in nm (10Ϫ3 × molar extinction coefficient at the maxi-
1
mum). H NMR spectra were recorded in CDCl3 on a Bruker
AC-250 at 250 MHz or a Bruker AM-400 spectrometer at 400
MHz. J values are in Hz.
11,12-Didehydro-â-carotene 3. To
a solution of 11,12-
didehydroretinal29 1 (4.32 g, 15.3 mmol) and retinyl(triphenyl)-
phosphonium bromide31 2 (9.08 g, 14.9 mmol) in 35 ml of
isopropyl alcohol under argon and at Ϫ25 ЊC were slowly
added 8.7 ml of a 10% solution of potassium hydroxide in iso-
propyl alcohol. After stirring for 30 min, the precipitate was
isolated by filtration and dried under vacuum at room temp.
The orange solid was then dissolved in refluxing hexane and the
triphenylphosphine oxide eliminated by filtration. The solvent
was evaporated and the residue triturated in cold hexane to
yield 3.6 g of crude 11,12-didehydro-β-carotene 3. Several
recrystallizations from ethyl acetate–hexane 1:1 gave 1.03 g
(13%) of 3 as a red solid, mp 135–136 ЊC (Calc. for C40H54: C,
89.82; H, 10.18%. Found: C, 89.38; H, 10.34%); MS m/z 534
(Mϩ, 54%), 519 (4%), 69 (100%); λ/nm 272 (18.8), 434 (113); δH
6.58–6.7 (2H, m, 11Ј, 14H), 6.5–6.52 (2H, m, 15,15ЈH), 6.35
(1H, d, J 15, 12ЈH), 6.25 (1H, d, J 17.5, 7H), 6.22 (1H, d, J 12.2,
14ЈH), 6.18 (1H, d, J 15.7, 7ЈH), 6.15 (1H, d, J 12.3, 10ЈH), 6.13
(2H, d, J 16, 8,8ЈH), 5.59 (1H, s, 10H), 2.07 (3H, s), 2–2.05 (4H,
m, 4,4ЈH), 1.99 (3H, s), 1.97 (6H, s), 1.72 and 1.7 (6H, 2s,
5,5ЈMe), 1.65–1.57 (4H, m, 3,3ЈH), 1.48–1.44 (4H, m, 2,2ЈH),
1.03 and 1.02 (12H, 2s, 1,1ЈMe).
Purification of 11-cis and 11,11Ј-di-cis-â-carotenes. Both the
11-cis and 11,11Ј-di-cis isomers as obtained with purities of 76
and 86% were then purified by HPLC using a Shimadzu LC-
10AS chromatograph and a Waters 996 photodiode-array
detector under the following conditions: column, a 4 mm
i.d. × 300 mm column packed with calcium hydroxide at 300
kg cmϪ2 (Nacalai Tesque Inc., Lot. M5M2325); eluent, 0.5%
acetone in n-hexane; flow rate, 0.5 ml minϪ1; and detection, 450
nm. An 8 mm i.d. column and higher flow rate of 1.5–3.0 ml
minϪ1 were used for collection and for tracing thermal isomeri-
zation of these isomers (vide infra).
11-cis-â-Carotene 4. To a solution of 11,12-didehydro-β-
carotene 3 (0.5 g, 0.9 mmol) in 25 ml of dry tetrahydrofuran
(THF) were added 0.5 g of Lindlar catalyst and 0.25 g of
sodium carbonate. The reaction mixture was hydrogenated at
Ϫ15 ЊC and at 1 atm for 6 h and then filtered over aluminium
oxide. The concentration of the solvent under vacuum at 20 ЊC
gave 417 mg crude material containing 9% 3, 13% all-trans-β-
carotene and 76% 11-cis-β-carotene33 4. It was purified by pre-
parative HPLC (vide infra).
Electronic absorption and Raman measurements
The electronic absorption spectra of isomeric β-carotene were
recorded at room temp. in n-hexane solution on a Hitachi
U-2000 spectrophotometer. The extinction coefficients were
determined by the use of ca. 13.5–21.8 mg of isomeric β-
carotene (all-trans, 15-cis, 11-cis and 11,11Ј-di-cis) in n-hexane;
the mass of each sample was measured to an accuracy of 0.1
mg and then the electronic absorption at the maximum of the
all-trans-[3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-
enyl)nona-2,6,8-trien-4-ynyl]triphenylphosphonium bromide 5. A
solution of 11,12-didehydroretinol,29a,c,30 (14.22 g, 50 mmol) in
190 ml of ethyl acetate was treated at Ϫ20 ЊC with phosphorus
tribromide (5.42 g, 20 mmol) in 50 ml of ethyl acetate. The
reaction mixture was stirred for 1 h and ice–water (250 ml) was
then cautiously poured into the reaction mixture. The organic
phase was separated and the water phase again extracted with
100 ml of ethyl acetate. The organic phases were combined,
washed with saturated sodium hydrogen carbonate and brine,
and dried over anhydrous sodium sulfate. Triphenylphosphine
(14.7 g, 56 mmol) was added to the filtered solution which was
stirred overnight at room temp. The solvent was evaporated and
120 ml of acetone–diethyl ether 1:1 added to the orange
residue. The mixture was then stored at 0 ЊC and the precipitate
filtered, washed with cold diethyl ether and dried under vacuum
to yield crude phosphonium salt 5. Recrystallization from
acetone–diethyl ether gave 10.5 g (34.5%) of 5 as a yellow
powder, mp 128–133 ЊC (decomp.); MS m/z 529 (Mϩ, 100%); δH
7.7–7.95 (15H, m, arom.), 6.27 (1H, d, J 16), 6.1 (1H, d, J 16),
5.71 (1H, dd, J 8), 5.45 (1H, s), 4.95 (2H, dd, J 8), 2.01 (2H, m),
1.99 (3H, s), 1.68 (3H, s), 1.6 (2H, m), 1.58 (3H, s), 1.47 (2H,
m), 1.0 (6H, s).
Ϫ
Buϩ←Ag absorption was determined after dissolving into,
and diluting with, n-hexane (0.3% of THF was used in the case
of the all-trans isomer for dissolving the crystals).
The Raman spectra of isomeric β-carotene were recorded at
liquid nitrogen temperature in n-hexane solution under a pre-
resonance condition (see Fig. 3) by the use of the 514.5 nm line
(1 mW) of a Lexel 95 Arϩ-ion laser and a JASCO TRS-300
Raman spectrometer which was equipped with a Princeton
Instruments IRY-700 detector.
NMR measurements
The 1H and 13C NMR spectra of isomeric β-carotene were
recorded at 8 ЊC in [2H6]benzene (CEA 99.6%) on a JEOL
JNM-A400 FT NMR spectrometer. The sample concentrations
1
were ca. 7.0 × 10Ϫ4–4.7 × 10Ϫ3 and ca. 1.2–1.6 × 10Ϫ2 for H
1
and 13C NMR measurements, respectively. (1) H NMR: The
digital resolution of each 1D spectrum was 0.24 Hz. The pulse
sequences for 2D measurements were as follows: 1H,1H-COSY,
90Њ–t1–90Њ–t2; long-range 1H,1H-COSY, 90Њ–t1–90Њ–∆–t2 with
∆ = 400 ms; and 1H,1H-ROESY, 90Њ–t1–τm–(spin-rock)–t2,
11,12,11Ј,12Ј-Tetradehydro-â-carotene 6. To a solution of
11,12-didehydroretinal29 1 (1.41 g, 5 mmol) and 11,12-
didehydroretinyl(triphenyl)phosphonium bromide 5 (3.05 g, 5
J. Chem. Soc., Perkin Trans. 2, 1997
2709
Hu, Ying
