A New Family of Enantiomerically Pure Smectic C* Liquid Crystals with a Bridged Chiral Biphenyl Core

Article abstract of DOI:10.1021/jo972143i

The synthesis of enantiomerically pure bridged biphenyl compounds, (-)-(R)-3,9-bis(4-(dodecyloxy)benzoyloxy)-5,7-dihydro-1,11-dimethyldibenzo[c,e] thiepine, 13, and (-)-(R)-3,9-bis(4-(dodecyloxy)benzoyloxy)-5,7-dihydro-1,11-dimethyldibenzo[c,e]- thiepin d

Full text of DOI:10.1021/jo972143i

J . Org. Chem. 1998, 63, 3895-3898
3895
A New F a m ily of En a n tiom er ica lly P u r e Sm ectic C* Liqu id
Cr ysta ls w ith a Br id ged Ch ir a l Bip h en yl Cor e
Guy Solladie´,* Philippe Hugele´, and Richard Bartsch
Laboratoire de Ste´re´ochimie associe´ au CNRS, ECPM, Universite´ Louis Pasteur, 1 rue Blaise Pascal,
67008-Strasbourg, France
Received November 24, 1997
Abstract. The synthesis of enantiomerically pure bridged biphenyl compounds, (-)-(R)-3,9-bis(4-
(dodecyloxy)benzoyloxy)-5,7-dihydro-1,11-dimethyldibenzo[c,e]thiepine, 13, and (-)-(R)-3,9-bis(4-
(dodecyloxy)benzoyloxy)-5,7-dihydro-1,11-dimethyldibenzo[c,e]-thiepin dioxide, 14, is described. This
is the first report of smectic C* mesophases with a rigid twisted biphenyl core and axial chirality.
We have recently reported1 a new family of enantio-
merically pure liquid crystals of type A and B showing
that molecules containing a rigid twisted biphenyl core
and axial chirality can give cholesteric mesophase (Figure
1). This result has confirmed our previous findings2
which showed that the mesomorphic character of sub-
stituted stilbenes was maintained when stilbenes were
converted to their epoxide, meaning therefore that the
planarity of the central aromatic core was not required
for mesomorphic behavior. In the oxepines A and B, the
presence of a bridge between the two aromatic rings is
certainly an important factor controlling particularly the
dihedral angle between the two aromatic rings (torsional
angle of 56°). It is well-known that in unbridged biphe-
nyls the introduction of ortho-substituents decreases
F igu r e 1.
strongly the mesophase thermal stability with disap-
pearance of the mesomorphic character3 as in the case
corresponding benzylic alcohol, and permanganate oxida-
tion to the carboxylic acid 3 which was then transformed
into the chiral oxazoline (-)-(S)-4, using the method
described by Meyers.6 Compound 4 was dimerized by the
Ullmann reaction with activated copper, affording a 58/
42 mixture of diastereomers 5 and 6. Meyers7 reported
that the Ullmann dimerization of chiral oxazoline of type
4, could give, under thermodynamic equilibrating condi-
tions, a diastereomeric enhancement and afford mainly
one diastereomer of the resulting biphenyl. When we
carried out the Ullmann dimerization of 4 in the condi-
tions described by Meyers we obtained indeed a nearly 1
to 1 mixture of the two diastereomers 5 and 6. We could,
however, separate these two diastereomers, (+)-(S,S,S)-5
and (-)-(R,S,S)-6, by silica gel chromatography in high
yield1,8 (Scheme 1).
The determination of the absolute configuration of 5
and 6 was achieved by chemical correlation1 of the
diastereomer (-)-(R,S,S)-6 to the known (+)-(R)-2,2′-
dihydroxy-4,4′-dimethoxy-6,6′-dimethylbiphenyl.9
The oxazoline (-)-(R,S,S)-6 was then hydrolyzed with
trifluoroacetic anhydride and acetylated to the diester
(-)-(R,S,S)-7 following the procedure of A. I. Meyers,6b
and reduced with LiAlH4 to the (+)-(R)-diol 8. Swern
oxidation to the (+)-(R)-dialdehyde 9, followed by hy-
drolysis of the methoxy groups with boron tribromide,
of tetra-o-chloro substituted biphenyls in which the
torsional angle is close to 90°. However, the size as well
as the polarity of the substituent may play a significant
role, since it was reported recently that o-fluorine sub-
stituents in octafluorobiphenyl derivatives do not prevent
the formation of mesomorphic compounds, a nematic
phase in this specific case.4
We report now in this paper the first examples of
smectic C* liquid crystals having the bridged enantio-
merically pure biphenyl structures 13 and 14. The
synthesis of the optically active targets 13 and 14 was
based on Ullmann coupling reaction of the chiral oxazo-
line (-)-(S)-4 (Scheme 1), a method developed by A.
Meyers.6,7
The synthesis of the diastereomeric oxazoline deriva-
tives 5 and 6 started from 4-bromo-3,5-dimethylmethoxy-
benzene (1) by selective bromination with NBS of one
methyl group, calcium carbonate5 hydrolysis to the
(1) Solladie´, G.; Hugele´, P.; Bartsch, R.; Skoulios, A. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 1533-1535.
(2) Solladie´, G.; Bartsch, R.; Zimmermann, R.; Gottarelli, G. Isr. J .
Chem. 1985, 25, 51.
(3) Byron, D. J .; Gray, W. G.; Worrall, B. M. J . Chem. Soc. 1965,
3706.
(4) Byron, D. J .; Matharu, A. S.; Wilson. R. C. Liq. Cryst. 1995, 19,
39-45.
(5) Smith, J . G.; Dibble, P. W.; Sandborn, R. E. J . Org. Chem. 1986,
51, 3762-3768.
(6) (a) Nelson, T. D.; Meyers, A. I. J . Org. Chem. 1994, 59, 2577-
80. (b) Meyers, A. I.; Meier, A.; Rawson, D. J . Tetrahedron Lett. 1992,
33, 853-856.
(8) We already reported in a short paper1 the chromatographic
separation of the biphenyloxazolines diastereomers 5 and 6. Unfor-
tunately in this paper the references to the pioneering work of Al
Meyers were accidently omitted. The authors apologize for this.
(9) Musso, H.; Steckelberg, W. Chem. Ber. 1968, 101, 1510-18.
(7) Nelson, T. D.; Meyers, A. I. Tetrahedron Lett. 1994, 35, 3259-
62.
S0022-3263(97)02143-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/15/1998

3896 J . Org. Chem., Vol. 63, No. 12, 1998
Solladie´ et al.
Sch em e 1
Sch em e 2
Sch em e 3
afforded the (+)-(R)-diphenol 10, which was esterified
with 4-(dodecyloxy)benzoyl chloride to the (+)-(R)-diester
11 (Scheme 2).
The aldehyde groups were then selectively reduced
with sodium borohydride into the diol (+)-(R)-12. Sub-
sequent iodination with chlorotrimethylsilane and so-
dium iodide and reaction with lithium sulfide gave the
target thiepine (-)-(R)-13. Finally the sulfur atom of 13
was oxidized with N-methyl-1,2-epoxy-1,2,3,4-tetrahy-
droisoquinolinium tetrafluoborate10 to the sulfone (-)-
(R)-14 (Scheme 3).
The phase transition temperatures (Table 1) of the
synthesized products were measured by differential
scanning calorimetry. The observed mesophases were
identified by optical microscopy and X-ray diffraction.
We reported for comparison the liquid crystal proper-
ties of the oxepines A and B1 (Table 1). We also made
by the same procedure two other oxepines with a para-
substituted C-12 chain on the aromatic rings instead of
a C-8 chain. This is usually an efficient way to obtain
smectic phases. As it is shown in the table we only got
lower cholesteric transition (enantiotropic mesophase for
A and monotropic for B).
In sharp contrast enantiomerically pure thiepine 13
and the corresponding sulfone 14 both displayed a
smectic C* phase. This is the first report of smectic C*
phases obtained from such twisted biphenyl structures.
The identification of these mesophases was made by
X-ray diffraction. Only the sulfur-bridged biphenyl
compounds 13 and 14 show a sharp Bragg reflection at
small angles which is characteristic of smectic layers. The
layer spacing determined by X-ray diffraction was 30.7
Å for 13 and 37.7 Å for 14. The length of the molecules
in their most extended conformations has been estimated
by molecular modeling (MOPAC software CAChe work
station from Oxford Molecular) to be about 52.6 Å for 13
and 52.2 Å for 14, these values being greater than the
layer spacing. Moreover, the layer spacing increased
with temperature, and it could be concluded that the
molecules are tilted in a smectic C* phase.
(10) Hanquet, G.; Lusinchi, X. Tetrahedron Lett. 1993, 34, 5299.
This oxidation failed with most of the usual oxidants.

Enantiomerically Pure Smectic C* Liquid Crystals
J . Org. Chem., Vol. 63, No. 12, 1998 3897
Ta ble 1. Tr a n sition Tem p er a tu r es of th e Liqu id Cr ysta ls
absol
config
transition
biphenyl
dihedral angle, deg
R
temp (deg)a
[R]D (acetone)
A, C8H17
A, C12H25
B, C8H17
B, C12H25
13, C12H25
14, C12H25
R
R
R
R
R
R
C 75 Ch 105 I
C 70 Ch 94 I
C (Ch 60) 78 I
C (Ch49) 58 I
C 71 Sc* 90 Ch 106 I
C 37 Sc* 42 Ch 46 I
56
56
56
56
63
58
+24 (c ) 1.6)
+20 (c ) 1.6)
-10 (c ) 2.0)
-10 (c ) 2.0)
-74 (c ) 2.0)
-45 (c ) 0.5)
a
C, Sc*, Ch, and I indicate crystal, smectic C, cholesteric phases, and isotropic solution. Numbers are the transition temperatures,
and numbers in parentheses indicate a monotropic transition which can be observed only in cooling the sample.
acidified (few drops of HCl) and then cleared by NaHSO3
Using MOPAC molecular modeling software, we de-
termined the dihedral angle of the bridged biphenyl
moiety in the minimum energy conformation: an angle
of 56° was already obtained for oxepines A and B; 63°
was calculated for the thiepine 13 and 58° for thiepine
dioxide 14.
solution. After addition of excess of NH4OH, the mixture was
passed through a short silica gel column to remove brown
precipitates, acidified with concentrated HCl, and extracted
with ether. After drying, the solvent was removed affording
16.4 g of acid 3 (86%): mp 129 °C; 1H NMR (200 MHz, CDCl3)
δ 10.3 (broad s, 1H), 7.25 (d, J ) 2.6 Hz, 1H), 6.98 (d, J ) 2.6
Hz, 1H), 3.82 (s, 3H), 2.45 (s, 3H); 13C NMR (50 MHz, DMSO-
d6) δ 167.95, 157.79, 139.89, 136.28, 118.19, 112.24, 111.65,
55.62, 23.13. Anal. Calcd for C9H9BrO3: C, 44.08; H, 3.67.
Found: C, 44.36; H, 3.70.
In conclusion, these new results confirmed that rigid
nonplanar and enantiomerically pure biphenyl deriva-
tives of type A or B can show liquid crystal properties.
It is clear at this point of our studies that an oxygen atom
on the bridge joining the two aromatic rings lead es-
sentially to cholesteric phases while a sulfur and a
sulfonyl group on the bridge lead to smectic C* phases.
This is probably the result of a higher transversal
polarization in the case of the sulfur compounds. This
was confirmed by the calculation of the dipolar moments
of the molecules containing only p-methoxy substituents
on the biphenyl core which gave 4.8 D for the cyclic
sulfone, 2.6 D for the thiepine, and only 1.9 D for the
oxepine. Moreover, a dihedral angle between 56° and 63°
seems to be an important factor for the mesomorphic
behavior.
(-)-(S)-4,5-Dih yd r o-2-(2-b r om o-3-m et h yl-5-m et h oxy-
p h en yl)-4-isop r op yl-1,3-oxa zole, 4. A mixture of the bro-
mobenzoic acid 3 (6 g, 24.5 mmol) and thionyl chloride (4.4
g,36.7 mmol) in benzene (50 mL) was heated under reflux for
3 h. The solvent and the excess of SOCl2 were removed in
vacuo, and the residue was dissolved in 50 mL of CH2Cl2 and
added to a cooled (0 °C) solution of (L)-valinol (2.8 g, 26.9
mmol), Et3N (10 mL), and CH2Cl2 (50 mL). The mixture was
stirred at room temperature overnight and washed with HCl
(2 M) and a saturated sodium bicarbonate solution. After
drying over sodium sulfate, the solvent was removed in vacuo
and the resulting solid purified by flash chromatography (ethyl
acetate/hexane: 8/2) to afford 6.78 g (20.6 mmol, 84%) of the
1
amide (S): mp 127 °C; H NMR (200 MHz, CDCl3) δ 6.83 (s,
2H), 6.2 (broad d, 1H), 3.9 (m, 3H), 3.78 (s, 3H), 2.4 (s, 3H),
2.0 (m, 1H), 1.0 (dd, J : 6.8 Hz, J : 1.4 Hz, 6H); 13C NMR (50
MHz, CDCl3) δ 169.1, 158.3, 140.1, 139.6, 117.7, 111.8, 111.6,
63.2, 57.5, 55.5, 29.0, 23.7, 19.6, 19.0.
Exp er im en ta l Section
2-Br om o-3-m eth yl-5-m eth oxyben zyl Alcoh ol, 2. A mix-
ture of 4-bromo-3,5-dimethylanisole (1)11 (86 g, 0.4 mol),
N-bromosuccinimide (71.2 g, 0.4 mol) and AIBN (0.2 g) was
refluxed in CCl4 (500 mL) for 4 h. The cooled reaction mixture
was washed with sat. NaHCO3, dried (MgSO4), and filtered,
and the solvent was evaporated to give crude 2-bromo-5-
methoxy-3-methylbenzylic bromide as a yellow solid (117.2 g,
85% yield determined by 1H NMR) which was used in the next
step without further purification. An analytical pure sample
was obtained by flash chromatography on silica gel (eluent:
hexane/ether: 80/20); mp 75 °C; 1H NMR (200 MHz, CDCl3) δ
6.85 (d, J ) 3 Hz, 1H), 6.77 (d, J ) 3 Hz, 1H), 4.61 (s, 2H),
3.80 (s, 3H), 2.41 (s, 3H); 13C NMR (50 MHz, CDCl3) δ 158.4,
140.4, 138.0, 117.6, 117.0, 114.0, 55.6, 34.8, 24.0.
To a cold solution (0 °C) of amide (6.6 g, 20 mmol) in 50 mL
of CH2Cl2 was added slowly a solution of SOCl2 (7.15 g, 4.36
mL, 60 mmol) in 50 mL of the same solvent. This mixture
was stirred for 2 h at 0 °C and then washed with an ice cold
sodium hydroxide solution (1 M) and saturated sodium bicar-
bonate solution. After drying over sodium sulfate, the solvent
was removed to yield 6.08 g (19.5 mmol, 98%) of the bromo
1
oxazoline 4 as a yellow liquid: [R]D -47.5 (c ) 2.0, EtOH), H
NMR (200 MHz, CDCl3): δ 6.96 (d, J ) 3.0 Hz, 1H), 6.86 (d,
J ) 3.0 Hz, 1H), 4.44 (m, 1H), 4.17 (m, 2H), 3.78 (s, 3H), 2.40
(s, 3H), 1.91 (oct., J ) 6.7 Hz, 1H) 1.06 (d, J ) 6.7 Hz, 3H),
0.99 (d, J ) 6.7 Hz, 3H); 13C NMR (50 MHz, CDCl3): δ 163.6,
158.1, 140.3, 131.8, 116.7, 114.6, 113.6, 72.9, 70.5, 55.5, 32.70,
23.9, 18.9, 18.4.
To a solution of the preceding bromide (60 g) in 1,4-dioxane
(500 mL) were added water (500 mL) and CaCO3 (100 g) and
the mixture refluxed for 12 h. After cooling, filtration of the
excess of CaCO3, and dioxane evaporation, CH2Cl2 (500 mL)
was added as well as diluted HCl to dissolve all the solids.
The organic layer was separated, washed with sat. NaHCO3,
dried (MgSO4), and filtered. After evaporation of the solvent,
the product was distilled under vacuum to give 36 g of 2 (90%
(+)-(S,S,S)- a n d (-)-(R,S,S)-4,4′-Dim et h oxy-6,6′-d i-
m et h yl-2,2′-(4,5-d ih yd r o-4-isop r op yl-1,3-oxa zol-2-yl)b i-
p h en yl, 5 a n d 6. A mixture of the bromo oxazoline 4 (5 g,16
mmol) and 5 g of freshly activated copper in 30 mL of freshly
distilled DMF was heated at reflux for 3 h. After cooling, the
mixture was diluted with CH2Cl2 and washed with aqueous
ammonia until the copper has been completely removed. The
organic layer was washed with water and dried (MgSO4) and
the solvent removed to give a yellow oil. Flash chromatogra-
phy (ether/hexane: 20/80) over Et3N-pretreated silica gel
afforded 1.6 g (43%) of the atropisomer (-)-(R,S,S)-6 (rf 0.22)
and 1.1 g (31%) of (+)-(S,S,S)-7 (rf 0.32).
1
yield): mp 52 °C; H NMR (200 MHz, CDCl3) δ 6.9 (d, J ) 3
Hz, 1H), 6.74 (d; J ) 3 Hz, 1H), 4.72 (s, 2H), 3.8 (s, 3H), 2.39
(s, 3H); 13C NMR (50 MHz, CDCl3) δ 158.7, 141.1, 139.3, 115.6,
111.4; 65.4, 55.5, 23.5.
1H NMR of the (R,S,S) diastereomer (200 MHz, CDCl3) δ
7.14 (d, J ) 2.7 Hz, 2H), 6.86 (d, J ) 2.7 Hz, 2H), 4.05-3.6
(m, 6H), 3.84 (s, 6H), 1.95 (s, 6H), 1.54 (oct, J ) 6.7 Hz, 2H),
0.74 (d, J ) 6.7 Hz, 6H), 0.70 (d, J ) 6.7 Hz, 6H); 13C NMR
(50 MHz, CDCl3) δ 164.2, 158.1, 139.4, 132.1, 129.3, 118.0,
110.9, 72.5, 70.0, 55.4, 32.6, 20.6, 18.7, 18.1; [R]D -119.5 (c )
1.4, EtOH). Anal. Calcd for C28H36O4N2: C, 72.43; H, 7.7; N,
6.0. Found: C, 72.45; H, 7.66; N, 5.88.
2-Br om o-5-m eth oxy-3-m eth ylben zoic Acid , 3. To a
boiling solution of alcohol 2 (18 g, 78 mmol) in acetone (450
mL) was added dropwise a solution of KMnO4 (16,6 g, 105
mmol) in water (350 mL) in 30 min, and heating was continued
for another 0.5 h. The cooled, dark brown mixture was
(11) Edwards, J . D.; Cashan, J . L. J . Am. Chem. Soc. 1956, 78,
3821-3824.

3898 J . Org. Chem., Vol. 63, No. 12, 1998
Solladie´ et al.
1H NMR of the (S,S,S) diastereomer (200 MHz, CDCl3) δ
7.23 (d, J ) 2.8 Hz, 2H), 6.86 (d, J ) 2.8 Hz, 2H) 4.02-3.66
(m, 6H), 3.85 (s, 6H), 1.90 (s, 6H), 1.64-1.54 (oct, J ) 6.7 Hz,
2H), 0.82 (d, J ) 6.8 Hz, 6H) 0.75 (d, J ) 6.8 Hz, 6H); 13C
NMR (50 MHz, CDCl3) δ 164.1, 157.9, 138.9, 132.5, 129.2,
118.2, 111.1, 72.4, 70.0, 55.3, 32.8, 20.5, 18.8, 18.2; [R]D +29.5
(c ) 1.4, EtOH).
(+)-(R )-4,4′-Dim e t h oxy-6,6′-d im e t h ylb ip h e n yl-2,2′-
d im eth a n ol, 8. To a THF solution (100 mL) of (-)-(R,S,S)-6
(2.4 g, 5.2 mmol) were added H2O (4 mL), trifluoroacetic acid
(6 mL), and 32 g of Na2SO4, and this suspension was stirred
overnight at room temperature. After filtration, the solvent
was removed in vacuo and the orange oil dissolved in 80 mL
of CH2Cl2. To this solution were added pyridine (8 mL) and
acetic anhydride (8 mL), and the mixture was stirred at room
temperature overnight. After washing with 1 N HCl (3 × 50
mL) and then water (100 mL) and drying of MgSO4, the solvent
was removed giving 1.9 g (68%) of diester 7 as a white solid:
mp 165 °C; [R]D -60 (c ) 2, EtOH); 1H NMR (200 MHz, CDCl3)
δ 7.35 (d, J ) 2.7 Hz, 2H), 7.02 (d, J ) 2.7 Hz, 2H), 5.45 (d, J
) 9.0, 2H), 4.35-4.27 (dd, J ) 4.5 and J ) 11.6 Hz, 2H); 3.95-
3.73 (m, 4H), 3.88 (s, 6H), 1.95 (s, 6H), 1.89 (s, 6H), 1.44-1.33
(m, 2H) 0.84 (d, J ) 6.7 Hz, 12H); 13C NMR (50 MHz, CDCl3)
δ 168.0, 166.5, 158.3, 139.0, 132.4, 131.4, 120.0, 112.4, 65.4,
55.4, 53.5, 28.6, 23.2, 20.5, 19.4, 18.9.
Diester (-)-7 (650 mg, 1.11 mmol) was dissolved in 30 mL
of THF and cooled at 0 °C. LiAlH4 (338 mg, 8.90 mmol) was
added. After stirring for 2 h, the mixture was hydrolyzed with
saturated NH4Cl solution and acidified to pH 1 with 3 N HCl
solution. The product was extracted with ether and dried over
MgSO4 and the solvent evaporated. Purification by flash
chromatography with ethyl acetate as eluent afforded 320 mg
(1.05 mmol, 95%) of diol 8: mp 83 °C; [R]D +12 (c ) 1.8, EtOH);
1H NMR (200 MHz, CDCl3) δ 6.86 (d, J ) 2.5 Hz, 2H), 6.75 (d,
J ) 2.5 Hz, 2H), 4.13 (d, J ) 11.6 Hz, 2H), 3.98 (d, J ) 11.6
Hz, 2H), 3.80 (s, 6H), 1.8 (s, 6H); 13C NMR (50 MHz, CDCl3) δ
158.8, 140.3, 138.0, 130.0, 115.3, 111.7, 62.9, 55.2, 20.3. Anal.
Calcd for C18H22O4: C, 71.50; H, 7.27. Found: C, 71.35; H, 7.13.
(+)-(R)-4,4′-Dim et h oxy-6,6′-d im et h ylb ip h en yl-2,2′-d i-
a ld eh yd e, 9. To a solution of oxalyl chloride (0.28 mL; 3.17
mmol) in CH2Cl2 (10 mL) at -78 °C were added 0.45 mL (6.35
mmol) of DMSO. The reaction mixture was stirred for 30 min,
and then diol 8 (240 mg, 0.79 mmol) in CH2Cl2 (6 mL) was
added dropwise. After stirring for 30 min, the mixture was
allowed to warm to room temperature and then cooled once
more to -78 °C and Et3N (1.1 mL, 7.7 mmol) added dropwise.
After stirring for 1 h, the mixture was hydrolyzed at 0 °C with
4 mL of H2O, and the product was extracted with CH2Cl2,
washed with a saturated solution of NaCl, dried (MgSO4), and
purified by flash chromatography (ethyl acetate/hexane: 2/8),
giving 220 mg (93%) of the white solid 19: mp 30 °C, [R]D +30
(c ) 1.7, EtOH); 1H NMR (200 MHz, CDCl3) δ 9.54 (s, 2H),
7.39 (d, J ) 2.8 Hz, 2H), 7.13 (d, J ) 2.8 Hz, 2H), 3.90 (s, 6H),
1.94 (s, 6H); 13C NMR (50 MHz, CDCl3) δ 181.0, 159.6, 139.8,
136.2, 132.8, 123.2, 108.5, 55.6, 19.7. Anal. Calcd for C18H18O4:
C, 72.47; H, 6.03. Found: C, 72.28; H, 6.05.
(+)-(R)-4,4′-Dih yd r oxy-6,6′-d im et h ylb ip h en yl-2,2′-d i-
ca r boxa ld eh yd e, 10. To a solution of dialdehyde 9 (400
mg,1,41 mmol) in 30 mL of anhydrous CH2Cl2 was added 5.6
mmol of BBr3 (5.6 mL of a 1 M solution in CH2Cl2) at -78 °C.
The mixture was warmed slowly to room temperature and
stirred for 24 h. After pouring into water, the product was
extracted with ether and washed with aqueous 2 N NaOH.
The aqueous layer was acidified with 3 N HCl, and the
diphenol 10 extracted with ether and dried (MgSO4), and the
solvent removed to give 284 mg of a white solid (yield 90%):
mp 136 °C, [R]D +49 (c ) 1, acetone); 1H NMR (200 MHz,
CDCl3) δ 9.54 (s, 2H), 8.90 (s, 2H), 7.78 (d, J ) 2.5, 2H), 7.16
(d, J ) 2.5, 2H), 1.94 (s, 6H); 13C NMR (50 MHz, CDCl3) δ
192.0, 137.5, 132.7, 123.8, 123.0, 113.2, 112.8, 19.8.
white solid (yield: 71%): mp 114 °C; [R]D +18.5 (c ) 2, acetone);
1H NMR (200 MHz, CDCl3) δ 9.65 (s, 2H), 8.16 (d, J ) 8.29,
4H), 7.78 (d, J ) 2.1, 2H), 7.50 (d, J ) 2.1, 2H), 7.00 (d, J )
8.9, 4H), 4.06 (t, J ) 6.5, 4H), 2.06 (s, 6H), 1.84 (m, 4H), 1.56-
1.27 (m, 36H), 0.89 (t, 6H); 13C NMR (50 MHz, CDCl3) δ 164.6,
164.0, 151.4, 139.7, 136.5, 136.0, 132.5, 129.3, 121.0, 119.5,
114.6, 68.5, 32.0, 29.7, 29.5, 29.2, 26.1, 22.8, 19.9, 14.2. Anal.
Calcd for C54H70O8: C, 76.6; H, 8.27. Found: C, 76.70; H, 8.41.
(+)-(R)-4,4′-Bis(4-(d od ecyloxy)ben zoyloxy)-6,6′-d im eth -
ylbip h en yl-2,2′-d im eth a n ol, 12. To a solution of dialdehyde
11 (160 mg, 0.19 mmol) in a mixture of 15 mL of EtOH and 8
mL of CH2Cl2 was added 17.2 mg of NaBH4 (0.45 mmol). The
reaction mixture was stirred for 20 min and then quenched
with saturated NH4Cl. After addition of 15 mL of CH2Cl2, the
organic layer was decanted, washed twice with H2O, dried
(Na2SO4), and then evaporated. The crude product was
purified by flash chromatogaphy on silica gel (eluent: AcOEt)
to afford 130 mg (81%) of the diol 12: mp 121 °C; [R]D +7 (c )
2, acetone); 1H NMR (200 MHz, CDCl3) δ 8.15 (d, J ) 9.0, 4H),
7.27 (d, J ) 2.0, 2H), 7.13 (d,J ) 2.0, 2H), 6.96 (d, J ) 9.0,
4H), 4.27 (d, J ) 12.2, 2H), 4.15 (d, J ) 12.2, 2H), 4.04 (t, J )
6.5, 4H), 3.2 (sbroad, 2H), 1.93 (s, 6H), 1.83 (m, 4H), 1.6-1.2
(m, 36H), 0.88 (t, 6H); 13C NMR (50 MHz, CDCl3) δ 165.3,
163.7, 150.5, 140.7, 137.7, 134.6, 132.4, 122.6, 121.6, 120.0,
114.4, 66.4, 62.5, 32.0, 29.74, 29.70, 29.67, 29.48, 29.45, 29.22,
26.10, 22.79, 20.15, 14.2. Anal. Calcd for C54H74O8: C, 76.23;
H, 8.70. Found: C, 76.24; H, 8.63.
(-)-(R)-3,9-Bis(4-(d od ecyloxy)ben zoyloxy)-5,7-d ih yd r o-
1,11-d im eth yld iben zo[c,e]th iep in e, 13. To a solution of diol
12 (90 mg, 0.1 mmol) and NaI (33.3 mg, 0.22 mmol) in
acetonitrile (10 mL) was slowly added freshly distilled ClSiMe3
(25 mg, 0.22 mmol). After stirring overnight, a sodium
hydrogen sulfite solution was added and the diiodo compound
extracted with ether, affording 112 mg of a yellow liquid
(yield: 98.9%); [R]D +7.7 (c ) 2, acetone); 1H NMR (200 MHz,
CDCl3) δ 8.16 (d, J ) 8.9, 4H), 7.35 (d, J ) 2.2, 2H), 7.15 (d,
J ) 2.2, 2H), 6.99 (d, J ) 8.9, 4H), 4.23 (d, J ) 9.7, 2H), 4.11
(d, J ) 9.7, 2H), 4.05 (t, J ) 6.5, 4H), 2.8 (s, 6H), 1.83 (m, 4H),
1.5-1.2 (m, 36H), 0.89 (t, 6H); 13C NMR (50 MHz, CDCl3) δ
164.8, 163.8, 150.9, 138.7, 138.1, 133.8, 132.4, 123.6, 121.9,
114.5, 68.4, 62.5, 32.0, 29.7, 29.5, 29.1, 26.1, 20.4, 20.1, 14.2.
The diiodo compound (100 mg, 0.09 mmol) was dissolved in
a mixture of CH3CN (10 mL) and THF (10 mL) and stirred at
room temperature for 3 days with lithium sulfide (12.8 mg,
0.28 mmol). The solvent was removed and the residue poured
into water, extracted with ether, dried, and chromatographed
on silica gel (eluent AcOEt/hexane 20/80) to give pure 13 (65%
1
yield): [R]D -74 (c ) 2, acetone); H NMR (200 MHz, CDCl3)
δ 8.15(d, J ) 8.8, 4H), 7.12 (d, J ) 2.3, 2H), 7.05 (d, J ) 2.3,
2H), 6.98 (d, J ) 8.8, 4H), 4.05 (t, 4H), 3.32 (s, 4H), 2.15 (s,
6H), 1.83 (m, 4H), 1.5-1.2 (m, 36H), 0.89 (t, 6H); 13C NMR
(50 MHz, CDCl3) δ 165.0, 163.7, 150.8, 137.9, 137.0, 134.5,
132.4, 122.3, 121.6, 118.7, 114.4, 66.4, 32.2, 32.0, 29.8, 29.7,
29.5, 29.2, 26.1, 22.8, 20.0, 14.2. Anal. Calcd for C54H74O6S:
C, 76.19; H, 8.70. Found: C, 76.13; H, 8.76.
(-)-(R)-3,9-Bis(4-(d od ecyloxy)ben zoyloxy)-5,7-d ih yd r o-
1,11′-d im eth yld iben zo[c,e]th iep in Dioxid e, 14. To a solu-
tion of 21 mg of thiepin 13 in 5 mL of CH2Cl2 was added
N-methyl-1,2-epoxy-1,2,3,4-tetrahydroisoquinolinium tetraflu-
oborate (25.2 mg, 0.05 mmol). After stirring for 10 min, the
solvent was removed and the product flash chromatographed
on SiO2 (ether/hexane 40/60), affording 21 mg of thiepin 6,6′-
1
dioxide 14 (yield 96%): [R]D -45 (c ) 0.5, acetone); H NMR
(200 MHz, CDCl3) δ 8.15 (d, J ) 8.9, 4H), 7.28 (d, J ) 2.0,
2H), 7.25 (d, J ) 2.0, 2H), 6.99 (d, J ) 8.9, 4H), 4.06 (t, 4H),
4.02 (d, J ) 13.4, 4H), 3.90 (d, J ) 13.4, 2H), 2.22 (s, 6H), 1.84
(q, 4H), 1.6-1.2 (m, 36H), 0.89 (t, 6H); 13C NMR (50 MHz,
CDCl3) δ 164.7, 163.8, 161.1, 139.1, 134.5, 132.5, 130.1, 124.5,
121.7, 121.1, 114.5, 88.5, 57.8, 32.0, 29.7, 29.5, 29.2, 26.0, 22.8,
20.1, 14.2. Anal. Calcd for C54H72O8S: C, 73.6; H, 8.2.
Found: C, 73.42; H, 8.2.
(+)-(R)-4,4′-Bis(4-(d od ecyloxy)ben zoyloxy)-6,6′-d im eth -
ylbip h en yl-2,2′-ca r boxa ld eh yd e, 11. To a solution of 10 (85
mg, 0.317 mmol) in 15 mL of CH2Cl2 were added successively
DMAP (0.160 g, 1.3 mmol) and 4-(dodecyloxy)benzoyl chloride
(250 mg, 0.760 mmol). The reaction mixture was stirred
overnight and then worked up as usual, affording 190 mg of a
Ack n ow led gm en t. We would like to thank Dr. A.
Skoulioz and Benoit Heinrich for very helpful advice for
these studies.
J O972143I