Highly Efficient Chirality Inductors Based on (5RS,8RS)-trans-5,6,6a,7,8,12b- Hexahydrobenzo[c]phenanthrene-5,8-diol

Full text of DOI:10.1021/jo9704319

7044
J . Org. Chem. 1997, 62, 7044-7046
Ta ble 1. Helica l Tw istin g P ow er s (âM) of th e Ch ir a l
High ly Efficien t Ch ir a lity In d u ctor s Ba sed
on (5RS,8RS)-tr a n s-5,6,6a ,7,8,12b-
Hexa h yd r oben zo[c]p h en a n th r en e-5,8-d iol
Diester s 1c
a
b
entry
1
X
[R]20
(c)
âM
D
COCH3
(a ) -251.2 (0.3)
(b) +230.7 (0.9)
(a ) -177.5 (0.2)
(b) +207.9 (0.2)
7.70 ( 0.01
7.87 ( 0.03
7.77 ( 0.07
7.83 ( 0.04
J ulie Cheung, Leslie D. Field, and Sever Sternhell*
2
3
4
5
CO(CH2)2CH3
Department of Organic Chemistry, University of Sydney,
Sydney NSW, Australia 2006
CO(CH2)10CH3
(a ) -131.6 (0.5) 12.61 ( 0.14
(b) +156.1 (0.6) 12.10 ( 0.13
(a ) -110.0 (0.2) 59.3 ( 0.1
(b) +119.2 (0.1) 54.5 ( 0.1
CO-p-C6H4(CH2)6CH3
Received March 10, 1997
CO-p-(C6H4)2(CH2)6CH3 (a ) -72.9 (0.5) 147.9 ( 0.1
(b) +87.1 (0.3) 142.6 ( 0.1
In tr od u ction
In a previous paper,1 we described the preparation and
resolution of (5RS,8RS)-trans-5,6,6a,7,8,12b-hexahy-
drobenzo[c]phenanthrene-5,8-diol (1, X ) H), a novel
molecular template of the general shape depicted by
structure (2). Esterification of the resolved diols (1a , X
) H) and (1b, X ) H) with a variety of acyl chlorides
leads to a series of chiral molecules (2) with “rods” of
variable length and nature.
Chloroform was used as solvent for the optical rotation
measurements. The values are accurate to about 5% due to the
a
b
small size of samples used. Signs of âM were not determined.
c Measurements were taken at 22 °C.
5,6,6a,7,8,12b-hexahydro-1,12-dimethylbenzo[c]phenan-
threne-5,8-diol (1, X ) H) with acetic anhydride to give
the diacetate (1, X ) COCH3),1 and with the correspond-
ing acyl chlorides to give the remaining esters.
The X-ray crystal structure of the diacetate (1, X )
COCH3)1 indicated that the ester chains are in pseu-
doequatorial positions in relation to the helical frame-
work and are approximately coplanar, thus giving an
elongated shape. The ORTEP plot of the diacetate (1, X
) COCH3)1 has a remarkable similarity to the conforma-
tion derived from 1H NMR data,1 indicating that the
conformation of the diacetate (1, X ) COCH3) is the same
in solution (CDCl3) and in crystal form. All the remain-
ing diesters produced from the diol (1, X ) OH) were
assumed to adopt a similar shape on the basis of the
1
similarity of their H NMR data, in particular the vicinal
coupling constants of the protons on C5, C6, C6a, C7, and
C8 (see the Experimental Section).
It is possible to convert a nematic mesophase into a
chiral nematic (cholesteric) mesophase by the addition
of a chiral inducer2 and to express the chirality-inducing
power of the additive in terms of a molecular property,
âM.2 This paper deals with the determination of the âM
values of five derivatives of the diol 1, X ) H, in the well-
known2 nematic phase, N-(4-methoxybenzylidene)-4′-
butylaniline (MBBA) (3), to explore whether the chiral
The diesters were resolved directly using HPLC with
a chiral column (Regis Pirkle type 1-A chiral column)1 to
give the enantiomers 1a and 1b in high enantiomeric
purity (a single peak in HPLC using the same column),
and their helical twisting powers (âM) towards the ne-
matic phase MBBA were examined by the droplet
method.4 The parameter âM has been employed to define
the twisting ability of the chiral solute in the nematic
phase and is expressed as the inverse of the helical pitch
value (1/p) of the macrohelical structure for a given molar
solute concentration (c) by the relation: 1/p ) âMc. The
pitch values were obtained at a number of different
concentrations, and the inverse of the pitch values were
plotted against the molar solute concentration. âM values
were calculated as the slope of the line of best fit to the
data points. The molar concentrations of the chiral
solutes were generally between 0.5 and 5 mol %, at which
point, the addition of more solute destroyed the macro-
helical structures produced. There were no observable
temperature effects over the nematic range of MBBA.
The results are summarized in Table 1.
template could transfer chirality intermolecularly.
A
search of the literature revealed few effective2 (large âM)
chiral inducers except the very few compounds listed by
Heppke.3
This work describes the preparation of five inducers
of the general structure 2 synthesised from 1a , X ) H,
and 1b, X ) H.
Resu lts a n d Discu ssion
Assignment of absolute stereochemistry (that is, the
attribution of the letter a or b) was based on the sign of
A series of (5RS,8RS)-trans-5,6,6a,7,8,12b-hexahydro-
1,12-dimethylbenzo[c]phenanthrene-5,8-diyl diesters (1,
X ) COCH3, X ) CO(CH2)2CH3, X ) CO(CH2)10CH3, X )
CO-p-C6H4(CH2)6CH3, and X ) CO-p-(C6H4)2(CH2)6CH3)
were synthesized by esterification of (5RS,8RS)-trans-
[R]20 for entries 2-5 by analogy with entry 1, which is
D
based on crystallographic data.1 Significantly, all the
enantimers with negative specific rotation were eluted
first. However, if these assignments were wrong, it is
unimportant for the present purposes, as this work is
concerned only with the absolute values of âM. It is
(1) Cheung, J .; Field, L. D.; Hambley, T. W.; Sternhell, S. J . Org.
Chem. 1997, 62, 62.
(2) Solladie´, G.; Zimmermann, R. G. Angew. Chem. Int. Ed. Engl.
1984, 23, 348, and references cited therein.
(3) Heppke, G.; Lotzsch, D.; Oestreicher, F. Z. Naturforsch. 1986,
41a, 1214.
(4) Candau, S.; le Roy, P.; Debeauvais, F. Mol. Cryst. Liq. Cryst.
1973, 23, 283.
S0022-3263(97)00431-3 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 20, 1997 7045
purification: νmax (Nujol) 1785s cm-1
1H NMR (200 MHz,
;
gratifying to note that the âM values for each pair of a
and b are very close, thus giving further confidence in
the experimental accuracy of the determinations of the
inducing powers.
CDCl3) δ 0.89 (t, J ) 6.0, 3H), 1.18-1.36 (m, 16H), 1.63-1.77
(m, 2H), 2.88 (t, J ) 8.0, 2H).
Lauryl chloride (250 mg, 1.15 mmol) was added dropwise
over a 30 min period at rt to a solution of (5SR,8SR)-trans-
5,6,6a,7,8,12b-hexahydro-1,12-dimethylbenzo[c]phenanthrene-
5,8-diol (1, X ) H) (100 mg, 0.36 mmol) in dry pyridine (5 mL).
The reaction mixture was heated at 90 °C under nitrogen for
1 h. The solution was poured onto ice, stirred, and filtered.
The residue was purified by flash chromatography over silica
(eluant, CH2Cl2 (12%) in light petroleum) to give (5SR,8SR)-
trans-5,6,6a,7,8,12b-hexahydro-1,12-benzo[c]phenanthrene-5,8-
diyl dilaurate (1, X ) CO(CH2)10CH3) as the major fraction.
Recrystallization from ethanol gave white needles (120 mg,
61%): mp 53-56 °C; νmax (chloroform) 1728 (s) cm-1; λmax
(chloroform) 265.8 nm (log ꢀ, 2.84); 1H NMR (600 MHz, CDCl3)
δ 0.88 (t, J ) 7.5, 6H), 1.18-1.44 (m, 32H), 1.52 (s, 3H), 1.58
(ddd, J ) 12.8, 11.4, 11.4, 1H), 1.79-1.91 (m, 5H), 1.86-1.98
(m, 1H), 2.05 (s, 3H), 2.27 (ddd, J ) 12.5, 4.2, 3.6, 1H), 2.35
(ddd, J ) 12.8, 9.7, 9.7, 1H), 2.44 (t, J ) 7.5, 2H), 2.52 (t, J )
7.5, 2H), 3.86 (d, J ) 11.4, 1H), 5.98 (dd, J ) 11.4, 3.6, 1H),
6.15 (dd, J ) 9.7, 9.1, 1H), 6.90 (dd, J ) 8.0, 1.0, 1H), 7.10
(dd, J ) 7.5, 0.8, 1H), 7.12 (dd, J ) 8.0, 8.0, 1H), 7.14 (dd, J )
7.5, 0.8, 1H), 7.22 (dd, J ) 7.5, 7.5, 1H), 7.23 (dd, J ) 8.0, 1.0,
1H); 13C NMR (50 MHz, CDCl3) δ 12.1, 18.1, 18.7, 20.7, 23.1,
27.3, 27.5, 27.6, 29.9, 32.72, 31.9, 33.2, 33.7, 41.4, 66.9, 69.2,
118.8, 120.7, 123.5, 124.4, 127.1, 128.8, 130.6, 133.2, 135.0,
135.5, 137.5, 171.3, 171.8; MS (CI, NH3) m/ z 676.9 ((M +
NH4)+, 100). Anal. Calcd for C44H66O4: C, 80.2; H, 10.0.
Found: C, 80.4; H, 10.2.
It can be seen that while the extension of the “rods” in
structure 2 from two to four atoms produces no signifi-
cant increase in âM (entries 1 and 2), and the significant
lengthening involved in changing to the bis-laureate
(entry 3, rods of 12 atoms length) produces only a modest
increase. However, the “stiffening” of the rods without
any increase in the numbers of atoms (entry 4) produces
a dramatic increase of âM from ca. 12 to 57. The
incorporation of rods which are both longer (16 atoms)
and stiffer (entry 5) produces a further ca. three-fold
increase in âM to give a chiral inducer of the same order
of magnitude of âM as the “chiral dopants with unusual
twisting powers” reported by Heppke.3
We have thus synthesized a chiral molecular template
which can serve as a basis for the preparation of a series
of chiral inductors and appear to have determined a
relationship between structure (length and stiffness of
rods) and the twisting power âM.
Exp er im en ta l Section
(5SR,8SR)-tr a n s-5,6,6a ,7,8,12b-Hexa h yd r o-1,12-d im eth -
ylb en zo[c]p h en a n t h r en e-5,8-d iyl Dib u t yr a t e (1, X )
CO(CH2)2CH3). Butyric acid (9.6 g, 0.12 mol) was added
dropwise to thionyl chloride (10 mL) at reflux over a period of
30 min. When all of the acid had been added, the reaction
mixture was heated at reflux under nitrogen for 30 min. The
mixture was distilled and the fraction boiling between 70 and
100 °C was collected. Redistillation provided butyryl chloride
(11 g, 86%), bp 100-101 °C (lit.5 bp 101-102 °C). νmax
(chloroform) 1808 (s) cm-1; 1H NMR (200 MHz, CDCl3) δ 1.00
(t, J ) 6.0 Hz, 3H), 1.70-1.80 (m, 2H), 2.78 (t, J ) 7.8 Hz,
2H).
(5S R ,8S R )-t r a n s-5,6,6a ,7,8,12b -H e xa h yd r o-1,12-d i-
m eth ylben zo[c]p h en a n th r en e-5,8-d iyl Bis(4-h ep tylben -
zoa te) (1, X ) CO-p-C6H4(CH2)6CH3). 4-Heptylbenzoic acid
(3 g, 13.6 mmol) was added slowly to thionyl chloride (5 mL)
at reflux. The mixture was heated at reflux for 2 h under
nitrogen. The excess thionyl chloride was removed under
reduced pressure and the residue of 4-heptylbenzoyl chloride
(3.2 g, 100%) was used in the next step without further purifi-
cation: νmax (chloroform) 1777s cm-1 1H NMR (200 MHz,
;
CDCl3) δ 0.88 (t, J ) 6.8, 3H), 1.24-1.35 (m, 8H), 1.59-1.67
(m, 2H), 2.67 (t, J ) 7.5 , 2H), 7.30 (d, J ) 6.0, 2H), 8.04 (d, J
) 6.0, 2H).
(5SR,8SR)-trans-5,6,6a,7,8,12b-Hexahydro-1,12-dimethyl-
benzo[c]phenanthrene-5,8-diol (1, X ) H) (112 mg, 0.4 mmol)
was dissolved in dry pyridine (10 mL) which was held at 40
°C. Butyryl chloride (100 mg, 0.9 mmol) was added dropwise
to the solution and the mixture was heated at 40 °C under
nitrogen for 1 h. The solution was poured into cold water,
filtered, and the residue of (5SR,8SR)-trans-5,6,6a,7,8,12b-
hexahydro-1,12-dimethylbenzo[c]phenanthrene-5,8-diyl dibu-
tyrate (1, X ) CO(CH2)2CH3) (130 mg, 75%) was collected. An
analytical sample was recrystallised from methanol: mp 120-
124 °C; νmax (nujol) 1743 (m) cm-1; 1H NMR (600 MHz, CDCl3)
δ 1.01 (t, J ) 7.5, 3H), 1.05 (t, J ) 7.5, 3H), 1.53 (s, 3H), 1.58
(ddd, J ) 12.4, 11.4, 11.4, 1H), 1.72 (ddd, J ) 12.8, 9.1, 8.1,
1H), 1.70-1.75 (m, 2H), 1.75-1.80 (m, 2H), 1.86-1.98 (m, 1H),
2.06 (s, 3H), 2.27 (ddd, J ) 12.4, 4.1, 3.4, 1H), 2.35 (ddd, J )
12.8, 9.8, 9.8, 1H), 2.43 (t, J ) 7.5, 2H), 2.51 (t, J ) 7.5, 2H),
3.86 (d, J ) 11.3, 1H), 5.99 (dd, J ) 11.4, 3.4, 1H), 6.16 (dd, J
) 9.8, 9.1, 1H), 6.91 (dd, J ) 6.8, 1.1, 1H), 7.09 (dd, J ) 6.8,
1.1, 1H), 7.13 (dd, J ) 6.8, 6.8, 1H), 7.15 (dd, J ) 6.8, 1.1,
4-Heptylbenzoyl chloride (490 mg, 2.1 mmol) was added
slowly to a solution of (5SR,8SR)-trans-5,6,6a,7,8,12b-hexahy-
dro-1,12-dimethylbenzo[c]phenanthrene-5,8-diol (1, X ) H)
(200 mg, 0.7 mmol) in dry pyridine (7 mL). The reaction
mixture was heated at 90 °C under nitrogen for 5 h poured
onto ice, stirred, and filtered. The residue was purified by
flash chromatography over silica (eluant, CH2Cl2 (10%) in light
petroleum) to give 4-heptylbenzoic acid (110 mg) as the first
major fraction. The second major fraction, (5SR,8SR)-trans-
5,6,6a,7,8,12b-hexahydro-1,12-dimethylbenzo[c]phenanthrene-
5,8-diyl bis(4-heptylbenzoate) (1, X ) CO-p-C6H4(CH2)6CH3)
(366 mg, 75%), was obtained as a white solid. An analytical
sample was obtained by recrystallization from methanol: mp
118-120 °C; νmax (chloroform) 1707 (m) cm-1; λmax (chloroform)
244.1 nm (log ꢀ, 4.57); 1H NMR (600 MHz, CDCl3) δ 0.89 (t, J
) 7.5, 6H), 1.25-1.36 (m, 16H), 1.63 (s, 3H), 1.61-1.69 (m,
4H), 1.75 (ddd, J ) 12.4, 11.5, 11.5, 1H), 1.92 (ddd, J ) 13.2,
8.9, 8.4, 1H), 2.02-2.14 (m, 1H), 2.18 (s, 3H), 2.43 (ddd, J )
12.4, 4.3, 3.5, 1H), 2.39 (ddd, J ) 13.2, 9.8, 9.8, 1H), 2.67 (t, J
) 7.5, 2H), 2.70 (t, J ) 7.5, 2H), 3.99 (d, J ) 11.1, 1H), 6.26
(dd, J ) 11.5, 3.5, 1H), 6.42 (dd, J ) 9.8, 8.9, 1H), 6.95 (dd, J
) 8.0, 1.0, 1H), 7.13 (dd, J ) 8.0, 1.0, 1H), 7.15 (dd, J ) 8.0,
8.0, 1H), 7.22 (dd, J ) 8.0, 1.0, 1H), 7.28 (dd, J ) 8.0, 8.0,
1H), 7.37 (dd, J ) 8.0, 1.0, 1H), 8.05 (dd, J ) 8.0, 1.5, 4H),
8.13 (dd, J ) 8.0, 1.5, 4H); 13C NMR (50 MHz, CDCl3) δ 14.1,
20.2, 20.8, 22.7, 29.1, 29.2, 31.2, 31.8, 36.1, 34.1, 35.3, 35.8,
43.6, 69.4, 72.0, 121.1, 123.0, 125.6, 126.6, 129.2, 130.8, 127.6,
127.7, 128.6, 129.9, 132.7, 135.4, 137.2, 137.7, 138.8, 148.8,
149.0, 166.1, 166.5. Anal. Calcd for C48H58O4: 82.5; H, 8.3.
Found: C, 82.7; H, 8.6.
1H), 7.21 (dd, J ) 6.8, 6.8, 1H), 7.23 (dd, J ) 6.8, 1.1, 1H); 13
C
NMR (50 MHz, CDCl3) δ 13.7, 18.5, 18.6, 20.6, 20.7, 33.9, 35.2,
35.7, 36.5, 36.6, 43.4, 68.9, 71.2, 120.8, 122.6, 125.5, 126.4,
129.1, 130.8, 132.6, 135.2, 137.0, 137.5, 138.6, 171.6, 172.0;
MS m/ z (relative intensity) 434 (M+, 20), 243 (100). Anal.
Calcd for C28H34O4: C, 77.4; H, 7.8. Found: C, 77.6, H, 8.0.
(5S R ,8S R )-t r a n s-5,6,6a ,7,8,12b -H e xa h yd r o-1,12-d i-
m eth ylben zo[c]p h en a n th r en e-5,8-d iyl Dila u r a te (1, X )
CO(CH2)10CH3). Lauric acid (20 g, 0.1 mol) was added
gradually to thionyl chloride (50 mL) and the mixture was
heated at reflux under nitrogen for 1 h. The excess thionyl
chloride was removed under reduced pressure. Lauryl chloride
was obtained as a clear oil (20.9 g, 86%) which was spectro-
scopically pure and was used in the next step without further
(5S R ,8S R )-t r a n s-5,6,6a ,7,8,12b -H e xa h yd r o-1,12-d i-
m et h ylb en zo[c]p h en a n t h r en e-5,8-d iyl Bis(4′-h ep t ylb i-
p h en yl-4-ca r boxyla te) (1, X ) CO-p-(C6H4)2(CH2)6CH3).
4-Heptyl-4′-cyanobiphenyl (Aldrich) (200 mg, 0.7 mmol) was
(5) Brown, H. C.; Ash, A. B. J . Am. Chem. Soc. 1955, 77, 4019.

7046 J . Org. Chem., Vol. 62, No. 20, 1997
Notes
added to sulfuric acid (6 M) maintained at 150 °C. The
mixture was heated for a further 3 h at 180 °C, cooled, and
filtered. The residue was added to a solution of sodium
hydroxide (2 M) and the precipitate of 4-heptyl-4′-biphenyl-
carboxylic acid was collected (176 mg, 85%): νmax (chloroform)
flash chromatography over silica (eluant, CH2Cl2 (10%) in light
petroleum) to give (5SR,8SR)-trans-5,6,6a,7,8,12b-hexahydro-
1,12-dimethylbenzo[c]phenanthrene-5,8-diyl bis(4′-heptylbi-
phenyl-4-carboxylate) (1, X ) CO-p-(C6H4)2(CH2)6CH3) (60 mg,
35%). An analytical sample was obtained by recrystallization
from toluene and methanol: mp 192-194 °C; νmax (chloroform)
1
1678 (m) cm-1; H NMR (200 MHz, CDCl3) δ 0.86 (t, J ) 6.8,
1
3H), 1.22-1.32 (m, 8H), 1.64-1.71 (m, 2H), 2.64 (t, J ) 7.5,
3H), 7.23 (d, J ) 8.0, 2H), 7.55 (d, J ) 8.0, 2H), 7.73 (d, J )
8.0, 2H), 8.23 (d, J ) 8.0, 2H); MS m/ z 296 (M+, 70), 211 (100).
Anal. Calcd for C20H24O2: C, 81.1; H, 8.1. Found: C, 80.7;
H, 8.3.
1708 (m) cm-1; H NMR (400 MHz, CDCl3) δ 0.89 (t, J ) 7.5,
6H), 1.24-1.36 (m, 16H), 1.61 (s, 3H), 1.62-1.69 (m, 4H),
1.75-1.84 (m, 1H), 1.93-2.01 (m, 1H), 2.06-2.14 (m, 1H), 2.14
(s, 3H), 2.46-2.58 (m, 2H), 2.65-2.69 (m, 4H), 4.02 (d, J )
11.1, 1H), 6.30 (dd, J ) 12.0, 4.0, 1H), 6.46 (dd, J ) 9.6, 8.4,
1H), 6.96 (d, J ) 7.7, 1H), 7.15-7.20 (m, 2H), 7.24-7.32 (m,
6H), 7.40 (d, J ) 7.6, 1H), 7.56 (d, J ) 7.6, 2H), 7.58 (d, J )
7.6, 2H), 7.69 (d, J ) 8.0, 2H), 7.74 (d, J ) 8.0, 2H), 8.19 (d, J
) 8.0, 2H), 8.28 (d, J ) 8.0, 2H); 13C NMR (50 MHz, CDCl3) δ
14.7, 20.8, 21.4, 23.3, 29.8, 29.9, 32.1, 32.4, 34.7, 36.0, 36.3,
36.5, 44.2, 70.2, 72.6, 121.7, 123.6, 126.3, 127.3, 127.6, 127.8,
129.3, 129.7, 129.9, 130.9, 131.5, 133.4, 136.0, 137.8, 137.9,
139.4, 144.0, 166.4, 167.2. Anal. Calcd for C60H66O4: 84.7;
H, 7.8. Found: C, 84.5; H, 7.6.
4-Heptyl-4′-biphenylcarboxylic acid (100 mg, 0.3 mmol) was
added slowly to thionyl chloride (10 mL) at reflux. The
mixture was heated at reflux for 3.5 h under nitrogen. The
excess thionyl chloride was removed under reduced pressure
and the residue of 4-heptyl-4′-biphenylcarbonyl chloride (94
mg, 100%) was used in the next step without further purifica-
tion: νmax (chloroform) 1775 (s) cm-1 1H NMR (200 MHz,
;
CDCl3) δ 0.88 (t, J ) 6.8, 3H), 1.26-1.37 (m, 8H), 1.58-1.66
(m, 2H), 2.69 (t, J ) 7.5, 2H), 7.27 (d, J ) 6.0, 2H), 7.54 (d, J
) 6.0, 2H), 7.73 (d, J ) 6.0, 2H), 8.15 (dd, J ) 6.0, 2H).
4-Heptyl-4′-biphenylcarbonyl chloride (94 mg, 0.3 mmol) was
added slowly to a solution of (5SR,8SR)-trans-5,6,6a,7,8,12b-
hexahydro-1,12-dimethylbenzo[c]phenanthrene-5,8-diol (1), X
) H (60 mg, 0.2 mmol) in dry pyridine (5 mL). The reaction
mixture was heated at 90 °C under nitrogen for 2.5 h, poured
onto ice, stirred, and filtered. The residue was purified by
Ack n ow led gm en t. The authors wish to express
thanks to the Australian Research Council and to the
Cooperative Research Centre for Molecular Engineering
and Technology for financial support.
J O9704319