Synthesis of deuterium-labelled, optically active, ferroelectric liquid crystals

Article abstract of DOI:10.1016/j.tet.2010.03.025

The synthesis of two selectively deuterium-labelled 4-(((S)-1-((S)-1-((S)-2-methylbutoxy)-1-oxopropan-2-yloxy)-1-oxopropan-2-yloxy)carbonyl)phenyl 4′-(heptyloxy)biphenyl-4-carboxylate derivatives is reported. A new preparation strategy was developed in or

Full text of DOI:10.1016/j.tet.2010.03.025

Tetrahedron 66 (2010) 3472–3477
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of deuterium-labelled, optically active, ferroelectric liquid crystals
,
,
a
A. Marini a b, V. Domenici a, C. Malanga a, R. Menicagli a , C.A. Veracini
*
a
`
Dipartimento di Chimica e Chimica Industriale, Universita degli studi di Pisa, via Risorgimento 35, 56126 Pisa, Italy
b Scuola Normale Superiore di Pisa, Piazza dei Cavalieri 7, 56126 Pisa, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of two selectively deuterium-labelled 4-(((S)-1-((S)-1-((S)-2-methylbutoxy)-1-oxopropan-2-
yloxy)-1-oxopropan-2-yloxy)carbonyl)phenyl 40-(heptyloxy)biphenyl-4-carboxylate derivatives is reported.
A new preparation strategy was developed in order to optimise the yields as well as the optical purity, this
property being of fundamental importance for the optical applications of this ferroelectric liquid crystal.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 28 October 2009
Received in revised form 15 February 2010
Accepted 8 March 2010
Available online 12 March 2010
Keywords:
Organic synthesis
Deuterium labelling
Ferroelectric liquid crystal
1. Introduction
impurities and stereochemistry. In particular, the synthesis of
ferroelectric mesogens with more than one chiral centre in one
Ferroelectric liquid crystals (FLCs)1 are very promising materials
for their technological applications,2 which are based on high and
selective responses to external electric and magnetic fields.3 The
relationship between the molecular properties and the macroscopic
physical properties of these liquid crystalline materials can be suc-
cessfully investigated by means of Nuclear Magnetic Resonance
(NMR) methods.4–6 In particular, Deuterium NMR (DNMR) spec-
troscopy applied to the study of liquid crystals has been proven to be
one of the most powerful tools for the investigation of FLCs meso-
morphic properties, molecular and conformational attributes.6 The
complete molecular characterisation of such systems usually ne-
cessitates the application of specific DNMR techniques to several
species, selectively deuterated in different sites of the molecule. For
instance, the availability of samples selectively deuterated on the
aromatic core of these FLC systems provides information (i.e., local
orientational ordering and molecular dynamics) concerning the
rigid moiety of the FLC molecule, which better mimics the whole
molecular behaviour of such anisotropic systems.4
of their terminal chains is very challenging.
New series of ferroelectric liquid crystals, having a flexible core
and one or more (up to three) chiral centres derived from (S)-lactic
acid,8 have been found to give very interesting properties. Recently,
a series of mesogen lactate-derivatives have been found to give
twist grain boundary (TGB) phases stable in a very wide tempera-
ture range,9,10 which is a rare phenomenon.
In this work, we have focused our attention on the chiral
ferroelectric 4-(((S)-1-((S)-1-((S)-2-methylbutoxy)-1-oxopropan-
2-yloxy)-1-oxopropan-2-yloxy)carbonyl)phenyl 40-(heptyloxy)-
biphenyl-4-carboxylate derivative (namely ZLL 7/
a rich polymorphism of ferroelectric phases, and the first re-entrant
SmC
found in bulk liquid crystal.11 The structural, orientational
*
), which shows
*
ordering and dynamic properties of this material have been char-
acterised thanks to the availability of selectively deuterium-labelled
compounds,12–14 which were in very good agreement with those
obtained by means of 13C NMR spectroscopy.15 Moreover, DNMR
investigation on selectively labelled ZLL 7/ derivatives revealed
*
The development of new and efficient synthetic routes for the
labelling of liquid crystals represents an essential and basic step in
the DNMR study of these systems. The rod-like ferroelectric liquid
crystals, one of the ordered soft materials most studied for their
technological applications, derive the property of ferroelectricity
directly from molecular chirality.1 Moreover, the high enantiomeric
selectivity is crucial in the appearance of the specific ferroelectric
subphases,7 which are extremely sensitive to both chemical
peculiar behaviours of the ferroelectric phase in the presence of
external magnetic fields of different intensities.16,17
2. Results and discussion
In this paper, we report the synthesis of two selectively labelled
4-(((S)-1-((S)-1-((S)-2-methylbutoxy)-1-oxopropan-2-yloxy)-1-
oxopropan-2-yloxy)carbonyl)phenyl 40-(heptyloxy)biphenyl-4-
carboxylate derivatives (Fig. 1), namely ZLL 7/
*
-phe-D2 (1) and
* Corresponding author. E-mail address: rime@dcci.unipi.it.
ZLL 7/ -biphe-D2 (2), respectively, in very good yields.
*
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.03.025

A. Marini et al. / Tetrahedron 66 (2010) 3472–3477
3473
Table 1
X
X
Interconversion of 7 into 8 via deuteration conditions
O
O
Y
Y
n.C7H15
O
O
T (ꢀC) t (h) Chemical Isotopic
Ref.
O
H
Me
O
Reaction condition
yielda (%) yieldb (%)
O
O
O
Me
1
2
3
4
5
DCl (5%)/D2O, DMF
DCl (5%)/D2O, DMSO
RhCl3$3H2O (10%)/D2O/DMF 130
DCl/D2O (1:1)
CF3COOD/D2O (1:1)
130
130
24
24
24
24
72
87
25
80
89
95
16
12
38
51
85
19
19
20
21
19
H
H
Me
Me
Figure 1. Molecular structure of the two isotopomers ZLL 7/
and ZLL 7/*-biphe-D2 (X¼D, Y¼H) (2).
*
-phe-D2 (X¼H, Y¼D) (1)
100
165
a
Overall yield.
b
Evaluated by 1H and 2H NMR spectroscopy.
A new synthetic strategy to prepare structural analogues of 1
and 2 was identified by a disconnection approach,16,17 reported in
Scheme 1. This synthetic strategy was followed, in a convergent
approach, in order to increase the chemical and isotopic yields,
with respect to previously reported procedures.18
Employing a Carius tube, at elevated temperature allows us to
reduce the reaction times, without the use of transition metal
catalysts.
X
O
O
Y
Y
n.C7H15
O
O
O
H
Me
O
X = H, Y =D 1
O
X = D, Y =H 2
X
O
O
Me
H
H
Me
H
Me
Y
Y
X
X
O
O
O
O
Me
O
X = H
X = D
3
Y = H
Y = D
5
6
HO
+
n.C7H15
O
O
4
O
Me
OH
H
H
H
Me
Me
X
X
Y
Y
O
Me
O
O
X = H
X = D
7
Y = H
9
O
11
+
HO
HO
HO
HO
HO
O
Me
8
Y = D 10
OH
OH
H
H
Me
O
Me
(X = D 8)
(X = D 10)
H
Me
O
Me
O
O
O
HO
Me
+
H
Me
OH
OH
O
12
O
H
9
13
7
Scheme 1. Disconnection approach for the preparation of compounds 1 and 2.
The regiocontrolled conversion of the commercially available 4-
(40-hydroxyphenyl) benzoic acid, (7) into the corresponding 8
(Scheme 1) carried out in acid catalysed conditions,19 was attemp-
ted using different experimental procedures reported in the litera-
ture for similar compounds (Table 1). As shown inTable 1 (runs 1–4),
even if satisfactory chemical yields (Runs 1, 3, 4) were gained, poor
(12/51%) conversions into the deuterated target 8 were obtained.
Compound 8 was obtained in a nearly quantitative chemical and
isotopic yield (Table 1, entry 5) when the reaction was carried out in
the presence of a 1:1 mixture of deuterotrifluoroacetic acid and
deuterium oxide.
Furthermore, this procedure could also be employed on a small
scale avoiding the use of cumbersome apparatuses (bench auto-
clave) ensuring a better recovery of crude reaction mixture.
Compounds 3 and 4 were easily obtained starting from 7 and 8,
respectively, under the experimental condition reported for anal-
ogous compounds18 (Scheme 1).
The commercially available 9 was regiochemically dideuterated,
in the presence of a 5% solution of DCl in D2O, to obtain compound
10 (93% yield) (Scheme 2) following the synthetic procedure
reported in literature.22
Compounds 9 and 10 were successively converted in the cor-
responding 4-(chlorocarbonyl) phenyl methyl carbonates 9b and
10b, respectively (Scheme 2), according to standard procedures.22
The use of CF3COOD instead of the DCl, in D2O, guarantees
a higher solubility of the reactants.
1) MeOCOCl, NaOH
SOCl2
MeOCOO
COOH
9a (92%)
MeOCOO
COCl
9b (100%)
2) H3O+
DMFcat
9
D
D
D
1) MeOCOCl, NaOH
2) H3O+
SOCl2
DCl (5%), D2O
100° C
10 (93%)
MeOCOO
COOH
MeOCOO
COCl
DMFcat
D
10a (90%)
10b (100%)
Scheme 2. Preparation of 4-methoxycarbonyloxybenzoyl chloride (9b) and the corresponding dideutero derivative (10b).

3474
A. Marini et al. / Tetrahedron 66 (2010) 3472–3477
The preparation, in low yields,8 of the known (3S,7S,10S)10-
chromatography 6890 Agilent, equipped with an HP-5MS fused
hydroxy-3,7-dimethyl-5,8-dioxa-6,9-undecandione
(11)
was
silica capillary column (stationary phase 5% diphenyl–95%
dimethyl-polysiloxane, 30 mꢃ0.25 mm) Hewlett Packard and with
a deactivated silica precolumn (2 mꢃ0.32 mm i.d., Agilent J.&W.)
and coupled to an Agilent 5975 Mass Selective Detector operating
obtained, in a 70% yield, via a more practical22 but strongly re-
vised12 procedure for analogous compounds (see Experimental and
Scheme 3).16
O
H
Me
O
12
n.BuLi, THF
O
O-Li+
Me
OH
Me
HO
O
Me
1) -78 − 0 °C
H
H
Me
Me
H
Me
Me
H
-78° C
2) H3O+
13
11 (70%)
Scheme 3. Preparation of (3S,7S,10S) 10-hydroxy-3,7-dimethyl-5,8-dioxaundecan-6,9-dione (11).
Preparation of 5 and 6, direct precursors to 1 and 2, respectively,
was carried out reacting 11 (Scheme 1) with the suitable aromatic
acyl chloride 9b or 10b (Scheme 4). Compounds 5a and 6a, re-
covered in 91 and 93% yields, were converted into 5 and 6 in 93 and
92% yields, respectively, by deacetylation, performed at ꢁ20 ꢀC, in
the presence of an equimolar amount of a 30% aqueous ammonia
solution (Scheme 4).
in electron impact mode (EI) at 70 eV. Mass spectra of 1 and 2
were carried out by Applied BioSystems-MDS Sciex API 4000 triple
quadrupole mass spectrometer (Concord, Ont., Canada), equipped
with a Turbo-V Ion Spry (TIS) source and interfaced to Perkin
Elmer Series 200 Micro HIGH Pressure mixing pump and a Series
200 autosampler (Perkin Elmer, Boston, MA, USA), was used for
LC/MS/MS analysis.
Y
O
1) Py
H2O/NH3
-20 °C
O
5 (93%)
or
H
Me
O
+ 11
9b (or 10b)
MeOCOO
O
2) NH4Cl
O
O
Me
6 (92%)
Y
H
H
Me
Me
Y = H 5a (91%)
Y = D 6a (93%)
Scheme 4. Preparation of (3S,7S,10S) 10-(40-hydroxy)benzoyloxy-3,7-dimethyl-5,8-dioxaundecan-6,9-dione (5) and the corresponding 30,50-dideutero derivative (6).
The coupling of 5 with 4 and 6 with 3, respectively, was per-
formed in good yields (75%) with dicyclohexylcarbodiimide
(2 mol equiv), in the presence of a catalytic amount of di(methyl-
amino)pyridine in a CH2Cl2 solution. The opticallyactive S precursors
used were ꢂ99% stereochemically pure and the reaction pathways
employed were stereospecific. HPLC analyses by means of chiral
phases of the compounds synthesised showed a satisfactory and
comparable optical purity level for both isotopomers 1 and 2.
1H and 13C NMR (300 and 75 MHz, respectively) characterisation
spectra were recorded on a Varian VXR 300 spectrometer; all NMR
data were obtained using CDCl3 solutions, if not otherwise stated.
Chemical shifts (
internal standard. IR spectra (
d
) are referenced to tetramethylsilane (TMS) as
n
, cmꢁ1) were recorded on a Perkin
Elmer FT-IR, 1760X spectrophotometer.
Compounds 7 and 12 (FlukaÒ) were used without further pu-
rifications. (S) 2-Methylbutanol (13) was accurately distilled to
obtain a 97.6% optical purity. 4-Di(methylamino)pyridine (DMAP)
and dicyclohexylcarbodiimide (DCCI) (FlukaÒ) were used as re-
ceived. The D2O (99.98 atom% D), and DCl 35 wt % in D2O, 99.00
atom% D, CF3COOD 99.5 atom% D were furnished by AldrichÒ.
3. Conclusion
This paper describes the first high yield deuterium labelling
chiral liquid crystals preparation of the two isotopomers 1 and 2.
These ferroelectric liquid crystals, having a most fascinating
aspect in the Science of Material field, were prepared by a stereo
conservative approach with high percentage of deuteration with an
almost complete regioselectivity.
4.1.1. 4-(30,50-Dideutero-40-hydroxyphenyl)benzoic acid (8). A Carius
tube containing 4-(40-hydroxyphenyl)benzoic acid (7) (1.00 g,
4.66 mmol), D2O (4 mL) and CF3COOD (4 mL) was warmed at
165 ꢀC, under stirring for 96 h. The reaction mixture was filtered off
at room temperature and the solid recovered, washed with a small
amount of D2O and dried at 50 ꢀC/0.05 mmHg. The recovered 8
(0.964 g, 95% yield) having mp 298–299 ꢀC (decomposition at
302 ꢀC) showed a 85% deuteration degree evaluated by 1H and 2H
NMR spectroscopy. Compound 8 showed:
4. Experimental
4.1. General procedures and materials
Solvents were purified and dried by standard procedures. GLC
analyses were performed on a Perkin–Elmer 8500 instrument [ZB1
IR (KBr): 3371, 2965, 1681, 1595, 1426, 1298, 1196, 1003, 830, 771,
715, 575, 490.
column (15 mꢃ0.25 mm), film 0.25
m
m] equipped with a flame
1H NMR (D2O, 200 MHz): 8.02 (d, 2H, 2-(CH)–o-COOH,
J¼8.4 Hz), 7.75 (d, 2H, 2-(CH)–m-COOH, J¼8.4 Hz), 7.62 (s, 2-(CH)–
m-OH, 2H). dD (H2O, 200 MHz): 6.94 (s, 2D). 13C NMR (D2O,
50 MHz): 164.7, 153.3, 146.5, 132.2, 131.0 (s, 2C), 128.6 (s, 2C), 127.1,
126.5 (s, 2C), 116.5 (t, 2CD).
ionisation detector and a split/splitless injector, with N2 as carrier
gas. Thin layer chromatography (TLC) analyses were performed on
silica gel 60 plates (Fluka) and purifications were carried out with
silica gel 60 (Fluka, 230–440 mesh). HPLC was carried out with an
Ecom High Performance Liquid Chromatography, using the Silica
Anal. Calcd for: C13H8D2O3: C, 72.21; HþD, 5.59%. Found: C,
Gel Column Separon 7
m
m, 150ꢃ3 mm, Tessek with a mixture of
72.19; HþD, 5.53%.
toluene and methanol as eluent. The CD (circular dichroism) data
registered for compounds 1 and 2 were recorded on a spec-
tropolarimeter Jasco J-40AS instrument, using CHCl3 as solvent.
Mass spectra of 4 and 5 (acquired after derivatization pro-
4.1.2. 4-(30,50-Dideutero-40-n-heptyloxyphenyl)benzoic acid (4). To
a
two-necked round bottom flask, containing KOH (0.767 g,
10.95 mmol), H2O (1,5 mL) and absolute ethanol (13.8 mL) under
cedure with BSTFA) were carried out by
a
GC–MS gas
stirring (15 min), 8 (1.00 g, 4.67 mmol) was added. The mixture was

A. Marini et al. / Tetrahedron 66 (2010) 3472–3477
3475
heated at reflux for 1 h. n-Heptyl bromide (1.55 mL, 9.86 mmol) and
KI (0.015 g) were added and the reaction mixture was heated at
reflux for 24 h. After cooling to room temperature, KOH (0.383 g) was
added and the mixture heated at reflux for further 12 h until com-
plete conversion of 8 into 4 (TLC analyses). After elimination of the
solvent, the crude product was poured into 200 mL of a H2O/H2SO4
1:1 solution and then extracted into Et2O/PhMe/CH2Cl2 (1:3:1, v/v).
The organic layer, dried with anhydrous Na2SO4, after the removal of
solvents at reduced pressure, gave 4 (1.30 g, 91% yield).
12.00 (s, –COOH, 1H), 8.18 (s, 2-(CH)–o-COOH, 2H), 3.95 (s, –CH3,
3H). 13C NMR: 171.6, 155.4, 153.7, 132.0, 127.2, 121.2 (t, 2CD), 120.6 (s,
2C), 55.9. Anal. Calcd for C9H6D2O5: C, 54.54; HþD, 5.09%. Found: C,
54.50; HþD, 5.04%.
4.1.6. 4-Methoxycarbonyloxybenzoic acid (9a). Compound 9a (92%
yield) was obtained starting from 4-hydroxybenzoic acid (9)
(1.04 g, 14.78 mmol), by using the same procedure employed to
prepare 10a. Compound 9a showed:
mp 181–182 ꢀC; IR (KBr): 2962, 1773, 1682, 1619, 1429, 1245,
1224,1047, 1032, 945, 773, 548. 1H NMR (CDCl3, 200 MHz): 12.00 (s,
–COOH, 1H), 8.14 (d, 2-(CH)–o-COOH, 2H, J¼8.4 Hz), 7.29 (d, 2-
(CH)–o-O–COOCH3, 2H, J¼8.4 Hz), 3.92 (s, –CH3, 3H). 13C NMR:
171.4, 155.5, 153.8, 132.2, 127.3, 121.4, 55.9.
Compound 4 showed:
mp 85 ꢀC; mesophases: 132 ꢀC(I)–225O227 C(II); isotropization
temperature 252 ꢀC.
IR (KBr): 3402, 3204, 2935, 2859, 2150, 1678, 1603, 1476, 1293,
1257, 1051, 835, 770, 541, 471. 1H NMR (CDCl3, 200 MHz): 11.55 (s,
COOH, 1H), 7.81 (d, 2-(CH)–o-COOH, 2H, J¼7.8 Hz), 7.64 (s, 2-(CH)–
m-OR, 2H), 6.94 (d, 2H, 2-(CH)–m-COOH, J¼7.8 Hz), 3.98 (1t, 2H, O–
CH2–, J¼6.5 Hz), 1.72 (2t, –O–CH2–CH2–, 2H, J1¼6.5 Hz, J2¼7.0 Hz),
1.33–1.28 (m, –(CH2)4–CH3, 8H), 0.85 (t, CH3, 3H, J¼6.4 Hz). 13C
NMR: 164.8, 153.4, 146.5, 132.2, 130.6 (t, 2CD), 128.2, 127.1, 126.5,
116.2, 68.9, 31.9, 29.7, 29.4, 26.0, 22.8, 14.1. Anal. Calcd for:
C20H22D2O3: C, 76.40; HþD, 8.34%. Found: C, 76.41; HþD, 8.30%.
Anal. Calcd for C9H8O5: C, 55.10; H, 4.11%. Found: C, 55.00; H,
4.10%.
4.1.7. (3S,7S,10S) 10-Hydroxy-3,7-dimethyl-5,8-dioxaundecan-6,9-
dione (11). A 100 mL three-necked flask, equipped with a magnetic
stirrer, a dropping funnel and a reflux condenser, under a nitrogen
25
atmosphere, containing (S) 2-methylbutanol ([
a
]
ꢁ5.77
D
o.p.¼97.6%) (1.009 g, 12.01 mmol) (13) and anhydrous THF (25 mL),
was cooled to ꢁ78 ꢀC. A 1.6 M hexane solution of BuLi (7.5 mL,
12.0 mmol) was added. The mixture was stirred for 20 min and
(3S,6S)-3,6-dimethyl-1,4-dioxan-2,5-dione (12) (1.72 g,11.96 mmol),
dissolved in anhydrous THF (10 mL), rapidly added. The mixture,
after 3 min, was siphoned into 150 mL of a 1% aqueous solution of
H2SO4 and 100 mL of Et2O, cooled to 0 ꢀC. The organic layer was
washed with an aqueous solution of saturated NaCl and dried over
anhydrous Na2SO4. After elimination of the solvent, the product was
purified by an accurate distillation. Chemically pure 11 (1.95 g, 70%
4.1.3. 4-(40-n-Heptyloxyphenyl)benzoic acid (3). Compound 3 (91%
yield) was obtained starting from 4-(40-hydroxyphenyl)benzoic
acid (7) (1.00 g, 4.66 mmol), by using the same procedure employed
to prepare 4. Compound 3 showed:
mp 85 ꢀC; mesophases: 132 ꢀC(I)ꢁ225O227 ꢀC(II); isotropiza-
tion temperature 252 ꢀC; IR (KBr): 2953, 2935, 2859, 1685, 1604,
1435, 1255, 835, 773, 551, 493.
1H NMR (CDCl3, 200 MHz): 11.42 (s, COOH, 1H), 8.05 (d, 2-(CH)–
o-OR, 2H, J¼8.2 Hz), 7.90 (d, 2-(CH)–o-COOH, 2H, J¼7.8 Hz), 7.67 (d,
2-(CH)–m-OR, 2H, J¼8.2 Hz), 6.82 (d, 2-(CH)–m-COOH, 2H,
J¼7.8 Hz), 3.98 (t, O–CH2–, 2H, J¼6.5 Hz), 1.72 (2t, –O–CH2–CH2–,
2H, J1¼6.5 Hz, J2¼7.0 Hz), 1.33–1.28 (m, –(CH2)4–CH3, 8H), 0.85 (t,
CH3, 3H, J¼6.4 Hz). 13C NMR: 164.8, 153.4, 146.6, 132.1, 130.7, 128.3,
127.2, 126.6, 116.1, 68.9, 31.9, 29.7, 29.4, 26.0, 22.8, 14.1.
Anal. Calcd for C20H24O3: C, 76.89; H, 7.74%. Found: C, 77.00; H,
7.70%.
yield) showed:
20
bp 110 ꢀC/2 mmHg; [
a]
ꢁ41.7 (neat); IR (neat): 3477, 2965,
D
2938, 2879,1743,1458,1380,1198,1132,1098,1049, 975, 866, 762. 1H
NMR: 5.15 (q, –CH–OR,1H, J¼7.0 Hz), 4.35 (q, –CH–OH,1H, J¼6.9 Hz),
4.02 (2dd, –CH2–O–, 2H, J1¼J2¼6.2 Hz), 2.80 (s, –OH, 1H), 1.60 (m,
CH3–CH–(CH2)2–, 1H), 1.52 (d, CH3–CH–OH, 3H, J¼7.0 Hz), 1.48 (d,
RO–CH–CH3, 3H, J¼7.0 Hz),1.42–1.24 (m, CH3–CH2–CH–, 2H), 0.91 (d,
CH3–CH–(CH2)2–, 3H, J¼6.6 Hz), 0.88 (t, CH3–CH2–, 3H, J¼6.4 Hz).13
C
4.1.4. 3,5-Dideutero-4-hydroxybenzoic acid (10). To a necked flask
containing D2O (165 mL) and DCl in D2O (27.36 mL), 9 (22.16 g,
160 mmol) was added. The mixture was heated at reflux for 48 h
and, after cooling, compound 10 spontaneously crystallised. The
solid was filtered off and washed with D2O (30 mL), and dried at
room temperature at 20 mmHg and successively at 70 ꢀC/
0.05 mmHg. The recovered 10 (20.72 g, 93% yield) having mp 219–
220 ꢀC showed a 98% deuteration degree, evaluated by 1H and 2H
NMR. Compound 10 showed:
NMR: 170.6, 170.3, 70.3, 65.7, 65.2, 55.8, 34.3, 26.1, 17.2, 16.5, 11.4.
Anal. Calcd for C11H20O5: C, 56.88; H, 8.68%. Found: C, 56.77; H,
8.63%.
4.1.8. (3S,7S,10S) 10-(30,50-Dideutero-40-methoxycarbonyloxy)benzoyl-
oxy-3,7-dimethyl-5,8-dioxaundecan-6,9-dione (6a). A 250 mL three-
necked round bottom flask, equipped with a magnetic stirrer,
a dropping funnel and a reflux condenser, under a nitrogen atmo-
sphere, containing 11 (3.32 g, 14.31 mmol), pyridine (6 mL) and
CH2Cl2 (15 mL) was cooled to 0 ꢀC. A solution of 3,5-dideutero-4-
methoxycarbonyloxybenzoyl chloride (10b)23 (2.79 g, 12.92 mmol)
in CH2Cl2 (25 mL) was slowly added and after stirring (24 h), the
mixture was hydrolysed with a 5% solution of HCl (100 mL),
extracted into CH2Cl2 and dried with anhydrous Na2SO4. The crude
oil, diluted in CH2Cl2 was purified by filtration on a short silica gel
column eluting with the same solvent (100 mL). Pure 6a (4.95 g,
93% yield) showed:
IR (KBr): 3285, 2990, 1678,1596, 1414, 1337, 1269, 1123, 768, 654,
540, 471.
1H NMR (D2O, 200 MHz): 7.87 (s, 2-(CH)–o-COOH, 2H), dD (H2O,
200 MHz): 7.12 (s, 2D). 13C NMR (D2O, 200 MHz): 162.4, 158.3, 131.2,
127.2 (s, 2C), 120.6 (s, 2C), 121.1 (t, 2CD, JCD¼42 Hz).
Anal. Calcd for C7H4D2O3: C, 59.99; HþD, 5.75%. Found: C, 60.10;
HþD, 5.70%.
4.1.5. 3,5-Dideutero-4-methoxycarbonyloxybenzoic acid (10a). In
a 250 mL Erlenmeyer flask cooled at 0 ꢀC, containing water (44 mL)
and NaOH (1,75 g, 43.75 mmol), 10 (2.04 g, 14.76 mmol) was added.
Methyl chloroformate (2.32 g, 24.56 mmol) was then added over
15 min to the homogeneous solution, under vigorous stirring. After
4 h, a 1:1 solution of HCl/H2O, was added until pH¼4–5. The mix-
ture was filtered off and the recovered 10 was washed with water
and then dried at reduced pressure (0.06 mmHg). Compound 10a
(2.59 g, 90% yield) showed:
IR (KBr): 2963, 2677, 1760, 1686, 1606, 1510, 1437, 1262, 941, 774,
550, 475.
1H NMR (CDCl3, 200 MHz): 8.17 (s, 2-(CH)–o-COOR, 2H), 5.38 (q,
–CH–OCOCH–, 1H, J¼6.9 Hz), 5.17 (q, –CH–OCOAr, 1H, J¼7.0 Hz),
4.02 (2dd, –CH2–O–, 2H, J1¼J2¼6.2 Hz), 3.95 (s, –CH3, 3H), 1.60 (m,
CH3–CH–(CH2)2–, 1H), 1.52 (d, CH3–CH–OCO–Ar, 3H, J¼7.0 Hz), 1.48
(d, R–COO–CH–CH3, 3H, J¼6.9 Hz), 1.42–1.24 (m, CH3–CH2–CH–,
2H), 0.91 (d, CH3–CH–(CH2)2–, 3H, J¼6.6 Hz), 0.88 (t, CH3–CH–-, 3H,
J¼6.4 Hz). 13C NMR: 170.6, 170.3, 165.3, 153.8, 131.9, 127.4, 120.6 (t,
2CD, JCD¼43 Hz), 70.3, 69.6, 65.3, 55.8, 34.3, 26.1, 17.2, 16.5, 11.4.
mp 181–182 ꢀC; IR (KBr): 2963, 1774, 1685, 1426, 1259, 1218,
1043, 1009, 941, 772, 648, 546, 475. 1H NMR (CDCl3, 200 MHz):

3476
A. Marini et al. / Tetrahedron 66 (2010) 3472–3477
Anal. Calcd for C20H24D2O9: C, 58.24; HþD, 6.84%. Found: C,
23.92 mmol), 6 (0.82 g, 23.96 mmol), DMAP (0.29 g, 2.38 mmol) and
58.20; HþD, 6.86%.
CH2Cl2 (50 mL) were placed, under N2, into a two-necked flask
equipped with a magnetic stirrer and a reflux condenser. The mixture
was stirred for 10 min and then DCCI (0.96 g, 46.28 mmol) was
added. After 2 h no more traces of 3 and 6 were detected (TLC). After
filtration on silica gel and elimination of the solvent by reduced
pressure, chemically pure (HPLC, NMR) 1 (1.20 g, 75% yield) was re-
4.1.9. (3S,7S,10S)
10-(40-Methoxycarbonyloxy)benzoyloxy-3,7-di-
methyl-5,8-dioxaundecan-6,9-dione (5a). Compound 5a (91% yield),
starting from compounds 9b24 and 11, was obtained by using the
same procedure employed to prepare 6a. Compound 5a showed:
IR (KBr): 2961, 2676,1775,1759,1687,1607,1509,1435,1261, 941,
774, 550.
covered. Compound 1 showed:
26.4
[
a
]
D
ꢁ4.6 (c 0.01085, CHCl3).
1H NMR (CDCl3, 200 MHz): 8.13 (s, 2-(CH)–o-O-COOCH3, 2H,
J¼8.2 Hz), 7.24 (d, 2-(CH)–o-COOR, 2H, J¼8.2 Hz), 5.38 (q, –CH–
OCOCH–, 1H, J¼6.9 Hz), 5.15 (q, –CH–OCOAr, 1H, J¼7.0 Hz), 4.02
(2dd, –CH2–O–, 2H, J1¼J2¼6.2 Hz), 3.95 (s, –O–COOCH3, 3H), 1.60
(m, CH3–CH–(CH2)2–, 1H), 1.52 (d, CH3–CH–OCO–Ar, 3H, J¼7.0 Hz),
1.48 (d, R–COO–CH–CH3, 3H, J¼6.9 Hz), 1.42–1.24 (m, CH3–CH2–CH,
2H), 0.91 (d, CH3–CH–(CH2)2–, 3H, J¼6.6 Hz), 0.88 (t, CH3–CH2–, 3H,
J¼6.4 Hz). 13C NMR: 170.6, 170.3, 165.4, 153.8, 131.6, 127.2, 120.4,
70.3, 69.5, 65.2, 55.8, 34.3, 26.1, 17.3, 16.5, 11.6.
CD spectra were recorded and showed a positive absorption
with a g factor (concentration 0.01674 mol/L in CHCl3) of:
g(310 nm)¼2.35ꢃ10ꢁ6; g(285 nm)¼2.66ꢃ10ꢁ6
.
IR (KBr): 2935, 2856, 1736, 1603, 1529, 1506, 1414, 1298, 1269,
1195, 1124, 1075, 829, 766, 691, 505. 1H NMR (CDCl3, 200 MHz):
8.31 (d, 2-(CH)–o-OR, 2H, J¼7.9 Hz), 7.80 (d, 2-(CH)–o-COOAr, 2H,
J¼6.4 Hz), 7.67 (d, 2-(CH)–m-OR, 2H, J¼7.9 Hz), 7.01 (s, 2-(CH)–o-
COOR, 2H), 6.94 (d, 2-(CH)–m-COOAr, 2H, J¼6.4 Hz), 5.29 (q, –CH–
OCOCH–, 1H, J¼6.9 Hz), 5.15 (q, –CH–OCOAr, 1H, J¼7.0 Hz), 4.02
(2dd, –OCH2–2H, J1¼J2¼6.2 Hz), 3.98 (t, ArO–CH2–, 2H, J¼6.5 Hz),
1.72 (2t, –O–CH2–CH2–, 2H, J1¼6.5 Hz, J2¼7.0 Hz), 1.69 (m, 4H), 1.55
(d, CH3–CH–OCO–Ar, 3H, J¼6.9 Hz), 1.54–1.23 (m, 10H), 0.91 (d,
CH3–CH–(CH2)2, 3H, J¼6.6 Hz), 0.88 (t, CH3–CH2–CH–, CH3–CH2,
CH2–, 6H, J¼6.4 Hz). 13C NMR: 170.8, 170.6, 165.4, 164.7, 159.9,
155.3, 146.6, 131.2, 131.1, 128.7, 127.2, 127.2, 126.5, 121.4 (t, 2CD o-
OH), 115.2, 70.3, 69.5, 65.3, 68.4, 34.3, 32.1, 29.5, 29.3, 26.2, 26.1,
22.5, 17.2, 16.5, 14.3, 11.4. m/z (TIS) 648 [Mþ, (16)], 647 [Mþꢁ1,
(92)], 646 [Mþꢁ2, (100)], 414 (7), 296 (27), 218 (6), 89 (7). Anal.
Calcd for C38H44D2O9: C, 70.35; HþD, 7.46%. Found: C, 70.40; HþD,
7.32%.
Anal. Calcd for C20H26O9: C, 58.53; HþD, 6.39%. Found: C, 58.58;
HþD, 6.30%.
4.1.10. (3S,7S,10S) 10-(30,50-Dideutero-40-hydroxy)benzoyloxy-3,7-
dimethyl-5,8-dioxaunde can-6,9-dione (6). A 100 mL Erlenmeyer
flask, containing EtOH (30 mL), H2O (30 mL) and 6a (1.00 g,
24.3 mmol), was cooled at ꢁ20 ꢀC. An equimolar amount of 30%
aqueous ammonia (0.25 mL) was added to the reaction mixture and
after stirring at room temperature for 18 h, TLC analysis showed the
complete conversion of 6a into 6. Solvents were removed under
reduced pressure and chemically pure 6 (GLC) (0.79 g, 92% yield)
was recovered. Compound showed 6:
IR (neat): 2961, 2878, 1732, 1597, 1496, 1275, 1089, 1056, 928,
862, 772, 625, 476.
4.1.13. 4-(((S)-1-((S)-1-((S)-2-methylbutoxy)-1-oxopropan-2-yloxy)-
1-oxopropan-2-yloxy)carbonyl)phenyl 30,50-dideutero-40-(heptyloxy)-
biphenyl-4-carboxylate (2). Compound 2 (77% yield) was obtained
from compounds (3S,7S,10S) 10-(40-hydroxy)benzoyloxy-3,7-di-
methyl-5,8-dioxaundecan-6,9-dione (5) (0.88 g, 23.96 mmol) and 4-
(30,50-dideutero-40-n-heptyloxyphenyl)benzoic acid (4) (0.75 g,
23.92 mmol), by using the same procedure employed to prepare 1.
1H NMR (CDCl3, 200 MHz): 10.26 (s, –OH,1H), 7.05 (s, 2-(CH)–m-
OH, 2H), 5.28 (q, –CH–OCOCH–, 1H, J¼6.8 Hz), 5.22 (q, –CH–OCOAr,
1H, J¼7.1 Hz), 4.02 (2dd, –OCH2–, 2H, J1¼J2¼6.3 Hz), 1.61 (m, CH3–
CH–(CH2)2–,1H),1.53 (d, CH3–CH–OCO–Ar, 3H, J¼7.1 Hz),1.48 (d, R–
COO–CH–CH3, 3H, J¼6.8 Hz), 1.42–1.24 (m, CH3–CH2–CH–2H), 0.91
(d, CH3–CH–(CH2)2, 3H, J¼6.7 Hz), 0.89 (t, CH3–CH2–, 3H, J¼6.4 Hz).
13C NMR: 170.4, 169.7, 155.3, 132.6, 131.9, 127.4, 121.8 (t, 2CD, o-OH),
70.3, 69.5, 65.3, 34.6, 26.2, 17.3, 16.7, 11.8. m/z (EI) 426 [Mþꢁ1, þ73,
(17)], 341 (4), 267 (6),195 (100), 73 (8). Anal. Calcd for C18H22D2O7:
C, 61.00; HþD, 7.40%. Found: C, 61.10; HþD, 7.36%.
The compound, chemically pure (HPLC, NMR), 2 showed:
30
[
a
]
D
ꢁ5.3 (c 0.01045, CHCl3).
CD spectra were recorded and showed a positive absorption
with a g factor (concentration 0.01612 mol/L in CHCl3) of:
g(310 nm)¼5.12ꢃ10ꢁ5; g(285 nm)¼5.54ꢃ10ꢁ5
.
IR (KBr): 2934, 2855, 1737, 1603, 1529, 1507, 1415, 1269, 1194,
1125, 1074, 829, 766, 691, 504. 1H NMR (CDCl3, 200 MHz): 8.31 (d,
2-(CH)–o-OCOAr, 2H, J¼7.8 Hz), 7.78 (d, 2-(CH)–o-COOR, 2H,
J¼7.8 Hz), 7.57 (d, 2-(CH)–o-COOAr, 2H, J¼6.3 Hz), 7.43 (s, 2-(CH)–
m-OR, 2H), 6.95 (d, 2-(CH)–m-COOAr, 2H, J¼6.3 Hz), 5.32 (q, –CH–
OCOCH–, 1H, J¼6.9 Hz), 5.16 (q, –CH–OCOAr, 1H, J¼7.1 Hz), 4.02
(2dd, –OCH2–, 2H, J1¼J2¼6.2 Hz), 3.98 (t, ArO–CH2–, 2H, J¼6.2 Hz),
1.72 (2t, –O–CH2–CH2–, 2H, J1¼6.5 Hz, J2¼7.0 Hz), 1.69 (m, 4H), 1.55
(d, CH3–CH–OCO–Ar, 3H, J¼6.9 Hz), 1.54–1.23 (m, 10H), 0.91 (d,
CH3–CH–(CH2)2, 3H, J¼6.6 Hz), 0.88 (t, CH3–CH2–CH–, CH3–CH2,
CH2–, 6H, J¼6.4 Hz). 13C NMR: 170.6, 170.4, 165.4, 164.7, 159.9,
155.3, 146.5, 131.8, 131.0, 128.6, 127.2, 127.1, 126.9, 122.1 (t, 2CD
o-OH), 115.2, 70.2, 69.4, 65.2, 68.3, 34.3, 32.2, 29.5, 29.3, 26.4, 26.1,
22.8, 17.1, 16.5, 14.3, 11.4. m/z (TIS) 648 [Mþ, (16)], 647 [Mþꢁ1,
(92)], 646 [Mþꢁ2, (100)], 414 (7), 296 (27), 218 (6), 89 (7). Anal.
Calcd for C38H44D2O9: C, 70.35; HþD, 7.46%. Found: C, 70.33; HþD,
7.50%.
4.1.11. (3S,7S,10S) 10-(40-Hydroxy)benzoyloxy-3,7-dimethyl-5,8-di-
oxaundecan-6,9-dione (5). Compound 5 (93% yield) was obtained
from (3S,7S,10S) 10-(40-methoxycarbonyloxy)benzoyloxy-3,7-di-
methyl-5,8-dioxaundecan-6,9-dione 5a (1.01 g, 24.30 mmol)
according to the same experimental procedure previously de-
scribed for compound 6. Compound 5 showed:
IR (neat): 2965, 2878, 1718, 1609, 1593, 1515, 1454, 1277, 1100,
852, 774, 625, 510.
1H NMR: 10.25 (s, OH, 1H), 7.98 (d, 2-(CH)–o-OH, 2H, J¼8.2 Hz),
6.95 (d, 2-(CH)–o-COOR, 2H, J¼8.2 Hz), 5.24 (q, –CH–OCOCH–, 1H,
J¼6.9 Hz), 5.15 (q, –CH–OCOAr, 1H, J¼7.0 Hz), 4.02 (2dd, –CH2–O–,
2H, J1¼J2¼6.2 Hz), 1.60 (m, CH3–CH–(CH2)2–, 1H), 1.52 (d, CH3–CH–
OCO–Ar, 3H, J¼7.0 Hz), 1.48 (d, R–COO–CH–CH3, 3H, J¼6.9 Hz),
1.42–1.24 (m, CH3–CH2–CH, 2H), 0.91 (d, CH3–CH–(CH2)2–, 3H,
J¼6.6 Hz), 0.88 (t, CH3–CH2–, 3H, J¼6.4 Hz). 13C NMR: 170.3, 169.5,
155.3, 132.3, 131.8, 127.4, 121.3, 70.3, 69.5, 65.2, 34.3, 26.1, 17.2, 16.5,
11.4. m/z (EI) 424 [Mþꢁ1, þ73, (17)], 339 (5), 265 (6),193 (100), 73
(6). Anal. Calcd for C18H24O7: C, 61.35; H, 6.86%. Found: C, 61.36; H,
6.90%.
Acknowledgements
4.1.12. 2,6-Dideutero-4-(((S)-1-((S)-1-((S)-2-methylbutoxy)-1-
oxopropan-2-yloxy)-1-oxopropan-2-yloxy)carbonyl)phenyl 40-(hep-
We would like to acknowledge Dr. J.J. Lucejko, Dr. A. Petri and
Prof. M. Zandomeneghi for their helpful advice and presence during
this investigation.
tyloxy)biphenyl-4-carboxylate (1). A mixture of
3
(0.75 g,

A. Marini et al. / Tetrahedron 66 (2010) 3472–3477
3477
13. Domenici, V.; Marini, A.; Menicagli, R.; Veracini, C. A.; Bubnov, A.; Glogarova, M.
Proceedings of SPIE – International Conference of Optics and Opto-electronics;
SPIE: Bellingham, 2007; Vol. 6587, pp F1–F13.
14. Domenici, V.; Marini, A.; Veracini, C. A.; Malanga, C.; Menicagli, R. Chem-
PhysChem 2009, 10, 2679.
15. Dong, R. Y.; Geppi, M.; Marini, A.; Hamplova, V.; Kaspar, M.; Veracini, C. A.;
Zhang, J. J. Phys. Chem. B 2007, 111, 9787.
16. Domenici, V.; Marini, A.; Veracini, C. A.; Dong. Zhang, R. Y. J. ChemPhysChem
2007, 8, 2575.
17. Warren, S. Organic, Synthesis: The Disconnection Approach; J. Wiley & Sons: New
York, NY, 2002.
18. Catalano, D.; Chiezzi, L.; Domenici, M.; Geppi, V.; Veracini, C. A. J. Phys. Chem. B
2003, 107, 10104.
19. Marini, A. LaureaThesis, University of Pisa, 2005.
20. Lockley, W. J. S. Tetrahedron Lett. 1982, 37, 3819.
References and notes
1. Musevic, I.; Blinc, R.; Zeks, B. The Physics of Ferroelectric and Antiferroelectric
Liquid Crystals, 1st ed.; World Scientific: Singapore, 2000.
2. Lagerwall, S. T. Ferroelectric and Antiferroelectric Liquid Crystals; Wiley-VCH:
Weinheim, 1999.
3. Kobayashi, K. K. J. Phys. Soc., Jpn. 1970, 29, 101.
4. Domenici, V.; Geppi, M.;Veracini, C. A. Prog. Nucl. Magn. Reson. Spectrosc. 2007, 50,1.
5. Dong, R. Y. Prog. Nucl. Magn. Reson. Spectrosc. 2002, 41, 115.
6. Veracini, C. A. In Nuclear Magnetic Resonance of Liquid Crystals; Emsley, J. W.,
Ed.; Reidel: Dordrecht, 1985.
7. Mach, P.; Pindak, R.; Levelut, A. M.; Barois, P.; Nguyen, H. T.; Wang, C. C.; Fur-
enlid, L. Phys. Rev. Lett. 1998, 81, 1015.
´
´
´
´
8. Kaspar, M.; Gorecka, E.; Sverenyak, H.; Hamplova, V.; Glogarova, M.; Pakhomov,
S. A. Liq. Cryst. 1995, 19, 589.
21. Finkelmann, H.; Ringsdorf, H.; Siol, W.; Endorff, J. H. W. ACS Symp. Ser.1978, 74, 22.
22. Watanabe, M.; Murakami, M. U.S. Patent 0,236,142 A1, 2004.
23. Previously prepared according to the usual procedure starting from 10a (2.56 g,
12.92 mmol), freshly distilled thionyl chloride (25 mL, 0.34 mol) and dime-
thylformamide (DMF) (300 mL).
24. Previously prepared according to the usual procedure starting from 9a (2.57 g,
9. Domenici, V.; Veracini, C. A.; Novotna, V.; Dong, R. Y. ChemPhysChem 2008, 9, 556.
10. Novotna, V.; Kaspar, M.; Domenici, V.; Hamplova, V.; Glogarova, M.; Bilkova, P.;
Pocieca, D. Liq. Cryst. 2008, 35, 287.
11. Kaspar, M.; Hamplova, V.; Novotna, V.; Glogarova, M.; Pocieca, D.; Vanek, P. Liq.
Cryst. 2001, 28, 1203.
12. Catalano, D.; Domenici, V.; Marini, A.; Veracini, C. A.; Bubnov, A.; Glogarova, M.
J. Phys. Chem. B 2006, 110, 16459.
12.97 mmol), freshly distilled thionyl chloride (25 mL, 0.34 mol) and dime-
thylformamide (DMF) (300 mL).