Discrimination of the enantiomers of new biphenylic derivatives in chiral micellar aggregates

Article abstract of DOI:10.1039/b610587d

The synthesis and characterization of two new chiral biphenylic derivatives is reported. The rotational barriers have been calculated on simpler homologues. The racemic mixtures of the two compounds have been used as probes of chirality for exploring the

Full text of DOI:10.1039/b610587d

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www.rsc.org/njc | New Journal of Chemistry
Discrimination of the enantiomers of new biphenylic derivatives in chiral
micellar aggregates
Francesca Ceccacci,a Luisa Giansanti,a Giovanna Mancini,*bc Paolo Mencarellia
and Alessandro Sorrentia
Received (in Durham, UK) 25th July 2006, Accepted 6th October 2006
First published as an Advance Article on the web 30th October 2006
DOI: 10.1039/b610587d
The synthesis and characterization of two new chiral biphenylic derivatives is reported. The
rotational barriers have been calculated on simpler homologues. The racemic mixtures of the two
compounds have been used as probes of chirality for exploring the sites of chiral recognition in
chiral micellar aggregates. Results suggest that one of the sites of chiral discrimination is the
hydrophobic part of the aggregates, far from the stereogenic centres.
The occurrence of a deracemization, resulting from different
Introduction
association constants of the enantiomers with the chiral
Assemblies formed by chiral amphiphiles have received atten-
aggregate, provides an opportunity to investigate chiral re-
tion over the last 30–40 years from different points of view.
cognition also by circular dichroism (CD). This may be an
They have been investigated by various approaches as chiral
important point in this type of investigation, because often
media for enantioselective reactions,1 used as selectors for
NMR fails to detect enantiodiscrimination due to broad
enantiomer separations2 and regarded as models for investi-
signals of surfactants under aggregating conditions. The bi-
gating the role of chirality in bio-membranes.3
phenylic derivatives we had previously used bear the hydro-
In the study of polymolecular aggregates as bio-membrane
phobic chain that binds the moiety to the aggregates in an
models it is of crucial interest to identify the non- covalent
ortho position. In order to further investigate the interactions
interactions responsible for the organization of the aggregates,
involved in the chiral recognition process in aggregates formed
for the transfer of the chiral information from the monomer to
by 1, we took into consideration, as chiral probes, two new
biphenylic derivatives, namely 2-carboxy-20-methoxy-40-N-do-
the aggregates and for aggregate recognition properties. We
have largely investigated micellar aggregates formed by so-
decyl-N-methylamino-6-nitrobiphenyl, 2a, and N,N-dimethyl-
dium N-dodecanoyl-L-prolinate, 1, as bio-membrane models
N-dodecil-N-[4-(2-methoxycarbonyl-6-nitrophenyl)-3-meth-
and found that they are capable of discriminating the enan-
tiomers of dipeptides3j and biphenylic derivatives3d,k used as
oxy]-phenylammonium bromide, 3a, both bearing a hydro-
phobic chain in a para position. Moving the hydrophobic
probes of chiral recognition. In fact, under aggregating con-
chain from an ortho to a para position should change the
ditions, the diastereomeric interactions between chiral assem-
orientation of the aromatic portion of the probe inside the
1
bly and probe enantiomers yielded diastereomeric H NMR
aggregates.
signals. The modulation of the molecular structure of the
Biphenyl derivative 2a features functional groups in the
chiral probe allowed us to tune the interactions with the
aggregates and to identify some sites of chiral recognition.3j,k
ortho positions that are known to determine a rotational
barrier that easily allows enantiomer interconversion at ambi-
In the case of biphenylic derivatives the choice of substituents
ent temperature as we found for 2-carboxy-20-methoxy-6-
and their position on the aromatic rings, besides determining
nitrobiphenyl, 4, for which a rotational barrier of 22 kcal
molꢀ1 was measured.4 The presence of a dialkylamino group
the mode of association and interaction with the aggregates,
also influences the rotational barrier. In the case of a suffi-
in the para position of 2a, should lead to an even lower barrier
ciently low rotational barrier the transfer of the chiral infor-
since it is known that the presence of an electron-donating
mation from the assembly to the probe may be revealed as an
substituent in the para position on one phenyl ring, combined
imbalance in the 1 : 1 equilibrium ratio of the interconverting
enantiomers of the probe, i.e. as a deracemization process.3i
with electron-withdrawing groups on the other, decreases the
rotational barrier of biphenyls.5
Biphenyl derivative 3a features a similar substitution pat-
a
tern, with two modifications: the presence of the carboxy-
methyl group instead of the carboxylic group and the presence
of a trialkyl ammonium group instead of the dialkylamino
group in the para position. Both modifications should sub-
stantially increase the rotational barrier with respect to 2a. The
former due to an increase of the steric hindrance at the ortho
positions, the latter because it is known that the presence of an
electron-withdrawing substituent in the para position en-
hances the rotational barrier.5
`
Dipartimento di Chimica, Universita degli Studi di Roma ‘‘La
Sapienza’’, P. le A. Moro 5, 00185 Roma, Italy.
E-mail: paolo.mencarelli@uniroma1.it; Fax: +3906490421;
Tel: +390649913078
b CNR, Istituto di Metodologie Chimiche, Dipartimento di Chimica
‘‘La Sapienza’’, P. le A. Moro 5, 00185 Roma, Italy.
E-mail: giovanna.mancini@uniroma1.it; Fax: +3906490421;
Tel: +390649913769
c Centro di Eccellenza Materiali Innovativi Nanostrutturati per
Applicazioni, Chimiche Fisiche e Biomediche, Via Elce di Sotto,
06123 Perugia, Italy
ꢁc
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Chart 1
Here we report on the preparation of 2a, and 3a, on the
gating conditions (i.e. in aqueous samples of (1) because of the
poor resolution of spectra below 292 K; moreover, the use of
other chiral auxiliaries did not yield well resolved diastereo-
meric signals. In view of the fact that the rotational barriers of
2a and 3a were experimentally not available to us, but con-
sidering that their knowledge is fundamental for the correct
interpretation of chiral recognition experiments, we decided to
evaluate the rotational barrier of their simpler homologues, 2b
and 3b, by theoretical calculation.
theoretical calculation of the rotational barriers for the simpler
homologues 2-carboxy-20-methoxy-40-N,N-dimethylamino-6-
nitrobiphenyl, 2b and N,N,N-trimethyl-N-[4-(2-methoxycar-
bonyl-6-nitrophenyl)-3-methoxy]-phenylammonium 3b, and
on the discrimination of biphenylic enantiomers of 2a, and
3a, in micellar aggregates formed by 1, observed by 1H NMR.
Results and discussion
In previous papers we showed that the rotational barrier of
a substituted biphenyl can be reliably evaluated by DFT
calculations at the B3LYP/6-31G(d) level of theory. The
results obtained for the rotational barriers, at such level of
theory, were in good agreement with the experimental va-
lues.3k,4 Our observation of the good behaviour of the DFT
approach was in accordance with results obtained by other
authors in the calculations of rotational barriers in biphenyls.7
Therefore the same DFT approach, at the same level of
theory, was used in this work for the calculations of the
rotational barriers of 2b and 3b (all the calculations were
carried out by using the Gaussian 98 or Gaussian 03
packages8).
Synthesis of biphenylic derivatives
Biphenylic derivatives 2a and 3a were prepared by mild
condition Ulmann coupling of 2-bromo-3-nitromethylbenzo-
ate with 5-N-dodecyl-N-methylamino-2-iodoanisole (Scheme
1). The following deprotection of the carboxylic group by
alkaline hydrolysis yielded derivative 2a, whereas quaterniza-
tion of the amino function with bromomethane yielded deri-
vative 3a. The halogenation of N-dodecyl-N-methyl-m-
anisidine according to a described procedure6 to yield 5-N-
dodecyl-N-methylamino-2-iodoanisole was regiospecific; halo-
genation of position 5 was verified by NOESY NMR experi-
ments.
The ground state structures and the transition states for the
enantiomerization of 2b and 3b were fully optimized, and each
stationary point found was characterized by a frequency
calculation. For the structures featuring one imaginary fre-
quency and therefore found to be a saddle point, the normal
mode corresponding to the imaginary frequency, was ani-
mated by using the visualization program Molden.9 In this
way it was verified that the displacements that compose the
mode lead to the two enantiomeric structures.
Theoretical calculation of the rotational barrier of biphenilic
derivatives
In the past we have measured the rotational barrier of
biphenylic derivatives by various techniques:3k,4 (a) by mea-
suring the racemization rate of one of the enantiomer after
separation by HPLC on a chiral phase at low temperature, (b)
by dynamic HPLC, exploiting the on-column racemization; (c)
by dynamic NMR, by investigating the response of diaster-
eomeric signals to temperature. In this work we did not
succeed in separating biphenylic enantiomers by HPLC, and
dynamic NMR experiments could not be performed in aggre-
For compound 2b six different minima were found for the
non-planar ground state (Fig. 1), and two different structures,
(E) and (Z), were found for the transition state of the
enantiomerization pathway (Fig. 2). The minima differ for
Scheme 1 Synthetic pattern. (i) Cu/DMF at 343 K; (ii) 10% NaOH under reflux; (iii) CH3Br in acetone.
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Fig. 1 Structures of the six minima found for 2b.
Fig. 3 Structures of the five minima found for 3b.
For compound 3b five different minima were found for the
non-planar ground state (Fig. 3), and four structures, two of
(E) configuration and two of (Z) configuration, were found for
the transition state of the enantiomerization pathway (Fig. 4).
The minima differ for the biphenyl dihedral angle and for the
rotation of the substituents. In particular, the more stable
minima 1 and 2 present the methoxycarbonyl moiety in the
more stable Z conformation, whereas minima 3, 4, and 5
present the less stable E conformation. This feature is also
found for the transition states in that in the least stable (E)-
TS2 transition state, the methoxycarbonyl moiety is in the less
Fig. 2 Structures of the two transition states found for the enantio-
merization of 2b.
the biphenyl dihedral angle and for the rotation of the sub-
stituents. In Table 1 total energies, relative energies and
biphenyl dihedral angles for the structures obtained from the
DFT calculations on 2b are reported.
Table 1 Total energies, relative energies and biphenyl dihedral angle
for the structures obtained from the DFT (B3LYP/6-31G(d)) calcula-
tions on 2b
E
rel/kcal
Dihedral angle,
degree
Ea (a.u.)
molꢀ1
Minimum 1
Minimum 2
Minimum 3
Minimum 4
Minimum 5
Minimum 6
(Z)-TS
ꢀ1104.5510 94
ꢀ1104.5502 16
ꢀ1104.5493 93
ꢀ1104.5489 34
ꢀ1104.5484 40
ꢀ1104.5470 84
ꢀ1104.5202 34
ꢀ1104.5153 58
0.00
0.55
1.07
1.36
1.66
2.52
19.36
22.42
126.1
125.5
73.2
ꢀ82.6
ꢀ116.5
ꢀ82.7
176.7
ꢀ1.9
(E)-TS
Fig. 4 Structures of the four transition states found for the enantio-
merization of 3b.
a
Zero-point corrections included.
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Table 2 Total energies, relative energies and biphenyl dihedral angle
for the structures obtained from the DFT (B3LYP/6-31G(d)) calcula-
tions on 3b
E
rel/kcal
Dihedral angle,
degree
Ea (a.u.)
molꢀ1
Minimum 1
Minimum 2
Minimum 3
Minimum 4
Minimum 5
(Z)-TS1
(Z)-TS2
(E)-TS1
(E)-TS2
ꢀ1183.475 232
ꢀ1183.474 762
ꢀ1183.457 565
ꢀ1183.457 448
ꢀ1183.457 031
ꢀ1183.433 711
ꢀ1183.433 187
ꢀ1183.433 047
ꢀ1183.421 584
0.00
0.29
ꢀ87.4
86.4
Fig. 5 Aromatic region of the 1H NMR spectrum of an aqueous
solution 4.0 mM in 2a and 40.0 mM in 1.
11.09
11.16
11.42
26.06
26.38
26.47
33.66
ꢀ92.4
86.0
92.4
176.6
177.8
ꢀ7.3
2.2
a
Zero-point corrections included.
stable E conformation. In Table 2 the total energies, relative
energies and biphenyl dihedral angles for the structures ob-
tained from the DFT calculations on 3b are reported.
Since six minima and two transition states were found for
2b, and five minima and four transition states were found for
3b, the rotational barriers for the enantiomerization of 2b and
3b, were obtained as the difference between the Boltzmann
averaged total energy of the transition states and the Boltz-
mann averaged total energy of the minima. The results are
reported in Table 3.
Fig. 6 Aromatic region of the 1H NMR spectrum of an aqueous
solution 4.0 mM in 3a and 40.0 mM in 1.
growth of the aggregates we obtain reasonable resolved
NMR spectra of the aqueous solutions, so that, in both cases,
we could observe splitting of some signals in the aromatic
region, due to the discrimination of biphenylic enantiomers by
the chiral micellar aggregates (Figs. 5 and 6). In fact, in the
spectrum relative to the aqueous solution of 2a the only triplet
we expect to observe is the signal due to the proton in position
4, whereas the spectrum reported in Fig. 5 shows two triplets
The values obtained for the rotational barriers confirm our
expectations (see above): the rotational barrier of 2b is 3 kcal
molꢀ1 lower than that of 4, whereas 3b features a barrier which
is 4 kcal molꢀ1 higher than that of 4. Our computational
finding thus agrees with what was experimentally known
about the effect of para substituents on the rotational barriers
of biphenyls.5 In order to illustrate the consequence of such
barriers on the enantiomerization rate, it is useful to translate
the barrier values into the corresponding reaction half-time
(t1/2). At 298 K, a rotational barrier of 19 kcal molꢀ1
corresponds to a t1/2 of about 1 s. In other words, the
racemization reaction of 2b is complete in about 10 s. At
variance, a rotational barrier of 26 kcal molꢀ1 corresponds, at
298 K, to a t1/2 of about 19 days; therefore, at room tempera-
ture, 3b requires more than 6 months to completely racemize.
These data should be taken into consideration when interpret-
ing the results of chiral recognition experiments in micellar
aggregates.
1
(at 7.05 and 7.52 ppm). 2D H NMR experiments allowed us
to assign signals as reported in Fig. 5, and therefore to assess
that the triplet at 7.05 ppm is due to the superimposition of
two diastereomeric doublets (in a B1 : 1 ratio) relative to the
protons in the 50 position (or 60) of enantiomeric biphenyls.w
1
Analogously, the H NMR spectrum relative to the aqueous
solution of 3a reported in Fig. 6 shows splitting of signals due
to protons in the 60 (or 50) position and to protons in the 30
position, still in a B1 : 1 ratio. Therefore experimental
evidence indicates that enantiomers of both biphenyls are
discriminated by the chiral micellar aggregates, however,
NMR evidence did not allow us to ascertain deracemization.
In fact, integration of NMR signals does not allow, generally,
the appreciation of small differences, moreover, due to the
small chemical shift differences in diastereomeric NMR sig-
nals, it was not possible to integrate them precisely.
Chiral recognition in micellar aggregates
Because enantiopure biphenylic derivatives feature high
molar ellipticities, even a small imbalance in the enantiomer
equilibrium may be easily revealed by circular dichroism
measurements. The CD spectra of the aqueous samples of 2a
and 3a in chiral micellar aggregates did not show any band
demonstrating the absence of any imbalance in the enantiomer
equilibrium.
Recognition experiments were carried out by 1H NMR and
Circular Dichroism on aqueous solutions of 4.0 mM bi-
phenylic derivative in the presence of 40.0 mM anionic surfac-
tant 1. The concentration ratio was such to allow a complete
solubilisation of the solute. Because the association of the
probes with the chiral aggregate did not induce excessive
Considering the relatively high rotational barrier that was
calculated for 3b, experimental evidence of an imbalance in the
enantiomer equilibrium, even in the presence of a differential
Table 3 Rotational barriers for the enantiomerization of 2b and 3b
obtained from the DFT (B3LYP/6-31G(d)) calculations
2b/kcal molꢀ1
3b/kcal molꢀ1
wBecause of line width enlargement, splitting of long range coupling
that allows a definite assignment in organic solvents is lost in aggre-
gating conditions.
19.00
26.13
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phobic chain (Chain and 11-CH3), demonstrating a preferen-
tial site of binding of the aromatic system in this region.
The finding of enantiodiscrimination in a hydrophobic site
of binding supports our hypothesis3j that chiral recognition
may occur in a chiral environment induced in an internal
region of the aggregate by remote stereogenic centers. In fact,
this result is in agreement with our previous observation of
enantiodiscrimination of dipeptides in the hydrophobic region
of aggregates formed by sodium N-dodecanoyl-L-prolinate.
Conclusions
We have explored the chiral recognition capabilities of a bio-
membrane model by using two new biphenylic derivatives as
probes of chirality. 1H NMR experiments allowed us to
observe enantiodiscrimination in both cases and to have
information on the sites of binding. The finding of enantio-
discrimination in a hydrophobic site of binding supports our
hypothesis that chiral recognition in polymolecular aggregates
might occur in a region of the aggregate remote from the
stereogenic centers. Therefore the translation of the chiral
information from the monomer to the aggregates is due to a
sum of recognition processes responsible of the organization
of the whole aggregate.
Fig. 7 1H NMR spectrum of (a) an aqueous solution 0.1 M in 1; (b)
an aqueous solution 0.1 M in 1 in the presence of 2a; (c) an aqueous
solution 0.1 M in 1 in the presence of 3a.
binding of the two enantiomers to the chiral micellar environ-
ment, was hardly expected. Therefore the absence of a band in
the CD spectrum of the aggregate solutions containing 3a does
not rule out the possibility that there is a differential binding.
On the other hand, considering that 2b features a rotational
barrier low enough to allow a very fast racemization, we could
reasonably expect that, should the interactions with the
aggregates favour the association of one enantiomer with
the aggregate, the transfer of the chiral information from the
aggregate to 2a could manifest itself as an imbalance of
the enantiomer equilibrium. Thus, the absence of a deracemi-
zation phenomenon in the aqueous solution of 2a in chiral
micellar aggregates, clearly indicates that there is no appreci-
able difference in the extent of binding of 2a enantiomers to
the chiral aggregates.
Experimental
2-Bromo-3-nitromethylbenzoate
The compound was prepared and characterized as previously
described.3d,10
N-dodecyl-m-anisidine
A mixture of 9.0 g (60 mmol) of m-anisidine and 6.3 g (25
mmol) of n-bromododecane in 20 mL of isopropanol was kept
under reflux until complete disappearance of the alkyl bromide
(B7 h), the reaction being monitored by TLC (SiO2, hexane).
After neutralisation with a saturated K2CO3 aqueous solution,
the mixture was extracted with Et2O and the organic solution
was washed with brine and then dried over Na2SO4. Removal
of solvent under reduced pressure gave a brown oil that, after
purification on silica gel (hexane/Et2O 95/5), yielded 6.3 g
(87%) of a white solid (m.p. found 305–307 K).
The effect of the aromatic systems of 2a and 3a on
the chemical shift of resonances due to 1 gives information
on the binding site of the chirality probe. In Fig. 7 we report
the comparison of the NMR spectrum of aqueous 0.10 M 1 in
the absence of solute (Fig. 7a) and in the presence of 2a (Fig.
7b) and 3a (Fig. 7c), respectively. The chemical shift differ-
ences (expressed in Hz) observed between the spectra per-
formed in the absence and in the presence of biphenylic
derivative are reported in Table 4. All resonances relative to
1 protons are upfield shifted due to the association of the
biphenylic derivatives with the aggregates; however inspection
of Table 4 suggests that there are differences in the site of
association of the two chirality probes, in fact in the case of 2a
the signal relative to a head group proton (dZanti) features the
highest chemical shift variation, demonstrating that this pro-
ton is in the shielding cone of the aromatic system. In the case
of 3a the most shifted signals are those relative to the hydro-
3
1H NMR (CDCl3) ppm: 0.885 (3H, t, CH3, J = 6.8 Hz);
1.268 (18H, m); 1.616 (2H, m, CH2); 3.083 (2H, t, N–CH2,
3J = 7.0 Hz); 3.769 (3H, s, O–CH3); 6.209 (3H, m, 2, 4, 6);
7.065 (1H, t, 5, Jo = 8.1 Hz).
N-dodecyl-N-methyl-m-anisidine11
A slurry of 1.1 g (3.8 mmol) of N-dodecyl-m-anisidine and 0.55
g (14 mmol) of NaBH4 in 10 mL of THF was added slowly to
an efficiently stirred solution of 0.9 mL of 37% aqueous
formaldehyde, 1.8 mL of 3M H2SO4 and 5 mL of THF at
263 K, keeping temperature below 293 K. After the evolution
of gas ceased, the solution was made strongly basic with
NaOH pellets and the supernatant was decanted and saved.
The white solid residue was treated with 20 mL of water and
the resultant solution was extracted with Et2O. The combined
organic solutions were washed with brine and dried over
Table 4 Chemical shift variations (Hz) of the signals due to the
aggregates formed by 1 in the presence of biphenylic derivative 2a
and 3a
anti
syn
dE
syn
dZ
a
dZ
1-CH2 2-CH2 Chain 11-CH3
1 + 2a 14 36
1 + 3a 11 25
10
8
22
25
22
20
20
19
18
30
17
29
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Na2SO4. Purification on silica gel (hexane/Et2O 95/5) of the
brown oil, obtained by removal of the solvent under reduced
pressure, gave 0.98 g (85%) of a pale yellow oil.
(around ambient temperature). 1H NMR (CDCl3) ppm: 0.875
(3H, t, CH3,); 1.200–1.380 (18H, m); 1.500–1.660 (2H, m,
CH2); 2.913 (3H, s, N–CH3,); 3.265 (2H, t, N–CH2, 3J =
7.3 Hz); 3.652 (3H, s, O–CH3); 6.259 (1H, d, 30, Jm = 1.8 Hz);
6.307 (1H, dd, 50, Jo = 8.5 Hz); 6.936 (1H, d, 60, Jo = 8.5 Hz)
7.428 (1H, t, 4, Jo = 7.9 Hz); 7.839 (1H, dd, 5, Jo = 8.1 Hz, Jm
= 1.1 Hz); 7.958 (1H, dd, 3, Jo = 8.1 Hz, Jm = 1.1 Hz).
13C NMR (CDCl3) ppm: 14.11; 22.67; 26.64; 27.14; 29.34;
29.47; 29.62; 29.65; 31.90; 38.82; 53.50; 55.08; 76.62; 77.04;
77.46; 96.21; 105.47; 112.28; 126.13; 127.08; 129.95; 132.39;
132.83; 134.94; 150.55; 151.13; 157.12; 171.57. Elemental
analysis calculated for C27H38N2O5: C 68.91%, H 8.14%, N
5.95%; found: C 69.70%, H 8.71%, N 5.61%.
3
1H NMR (CDCl3) ppm: 0.915 (3H, t, CH3, J = 6.4 Hz);
1.220–1.420 (18H, m); 1.586 (2H, m, CH2); 2.932 (3H, s,
3
N–CH3,); 3.300 (2H, t, N–CH2, J = 7.6 Hz); 3.811 (3H, s,
O–CH3); 6.309 (3H, m, 2, 4, 6); 7.149 (1H, t, 5, Jo = 7.9 Hz).
5-N-dodecyl-N-methylamino-2-iodoanisole6
A solution of 0.9 g (3.5 mmol) of I2 in 70 mL of CCl4 was
added over one hour, under inert atmosphere and in the dark,
to an heterogeneous mixture of 1.1 g (3.5 mmol) of N-dodecyl-
N-methyl-m-anisidine, 5 mL of CCl4, 0.35 g of CaCO3 and 16
mL of water. The reaction was monitored by TLC (SiO2,
hexane/Et2O 95/5). After 18 hours the organic phase was
washed with 7 mL of a saturated Na2S2O3 aqueous solution,
with brine and dried over Na2SO4. Removal of the solvent
under reduced pressure gave a dark yellow oil (in a 95% yield)
that was used immediately in order to avoid degradation.
N,N-dimethyl-N-dodecil-N-[4-(2-carboxymethyl-6-
nitrophenyl)-3-methoxy]-phenylammonium bromide, 3a
A solution of 0.12 g (0.025 mmol) of 2-carboxymethyl-20-
methoxy-40-N-dodecyl-N-methylamino-6-nitrobiphenyl in 3
mL of acetone was kept under stirring in a CH3Br saturated
atmosphere for seven days. The solution was then concen-
trated to one third of its volume and Et2O was added dropwise
until complete precipitation of a white solid (90% yield); m.p.
393–395 K.
1H NMR (CD3OD) ppm: 0.861 (3H, t, CH3); 1.060–1.600
(20H, m); 3.636 (3H, s, N–CH3); 3.742 (3H, s, OCH3); 3.850
(3H, s, COOCH3); 4.036 (2H, m, CH2); 7.287 (1H, d, Jo = 8.5
Hz); 7.450–7.540 (2H, m); 7.743 (1H, t, Jo = 7.9 Hz);
8.100–8.190 (2H, m).
3
1H NMR (CDCl3) ppm: 0.877 (3H, t, CH3, J = 6.3 Hz);
1.150–1.450 (18H, m); 1.556 (2H, m, CH2); 2.914 (3H, s,
3
N–CH3,); 3.276 (2H, t, N–CH2, J = 7.3 Hz); 3.844 (3H, s,
O–CH3); 6.094 (1H, dd, 4, Jo = 8.8 Hz, Jm = 2.5 Hz); 6.163
(1H, d, 6, Jm = 2.5 Hz); 7.466 (1H, d, 3, Jo = 8.8 Hz).
2-Carboxymethyl-20-methoxy-40-N-dodecyl-N-methylamino-6-
nitrobiphenyl
A solution of 1.4 g (3.2 mmol) of 5-N-dodecyl-N-methylami-
no-2-iodoanisole and 0.09 g (0.34 mmol) of 2-bromo-3-nitro-
methylbenzoate in 12 mL of anhydrous DMF was heated
gently in an inert atmosphere and 1.0 g of activated Cu0
powder was added when the temperature reached 343 K.
The reaction was monitored by TLC (SiO2, hexane/Et2O
6/4) and was complete after 3 hours. After filtration of the
reaction mixture, the solvent was removed under reduced
pressure and the residue dissolved in 100 mL of Et2O, treated
with 10% NH3 aqueous solution (2 ꢂ 5 mL), with brine and
dried over Na2SO4. After removal of the solvent under
reduced pressure, purification of the obtained brown oil on
silica gel (hexane/ Et2O 7/3) yielded 0.062 g (37%) of a red oil.
13C NMR (CD3OD) ppm: 14.40; 23.64; 24.31; 26.87; 29.53;
29.96; 30.25; 30.38; 30.53; 30.62; 53.01; 55.21; 55.29; 57.45;
70.64; 105.27; 114.01; 127.94; 128.78; 130.64; 131.36; 131.79;
134.68; 135.01; 146.93; 151.89; 159.45; 167.45; 211.69.
Elemental analysis calculated for C29H43BrN2O5: C 60.10%,
H 7.48%, N 4.83%; found: C 60.38%, H 8.11%, N 4.47.
Samples preparation
Samples of 4.0 mM biphenylic derivative in 40.0 mM aqueous
surfactant 1 were prepared by adding to the proper amounts of
surfactant and biphenylic derivative 0.700 mL of D2O. The
solutions were sonicated and gently heated to obtain clear
solutions.
3
1H NMR (CDCl3) ppm: 0.870 (3H, t, CH3, J = 6.6 Hz);
1.198–1.444 (18H, m); 1.500–1.700 (2H, m, CH2); 2.955 (3H, s,
3
N–CH3,); 3.305 (2H, t, N–CH2, J = 6.9 Hz); 3.641 (3H, s,
Acknowledgements
O–CH3); 3.683 (3H, s, COOCH3); 6.176 (1H, d, 30, Jm = 2.2
Hz); 6.274 (1H, dd, 50, Jo = 8.4 Hz, Jm = 2.2 Hz); 7.426 (1H,
t, 4, Jo = 8.1 Hz); 7.800–7.920 (2H, m, 3, 5).
This work has been carried out as part of the project ‘‘The use
of surfaces and vesicles for the amplification of homochirality
in polypeptide chains’’ of COST action D27. We acknowledge
contributions from CNR, Dipartimento di Progettazione
Molecolare.
2-Carboxy-20-methoxy-40-N-dodecyl-N-methylamino-6-
nitrobiphenyl, 2a
A solution of 0.14 g (0.29 mmol) of 2-carboxymethyl-20-
methoxy-40-N-dodecyl-N-methylamino-6-nitrobiphenyl in 3
mL of ethanol and 3 mL of 10% NaOH aqueous solution
was kept under reflux for 6 hours. The mixture was then
acidified to pH 4 with 3 M HCl and extracted with Et2O; the
organic phase was washed with brine and dried over Na2SO4.
After removal of the solvent under reduced pressure, purifica-
tion of the reddish oil on silica gel (hexane/AcOEt 1/1) yielded
0.13 g (96%) of a red solid that melts at a low temperature
References
1 (a) C. A. Bunton, L. Robinson and M. F. Stam, Tetrahedron Lett.,
1971, 121–124; (b) J. M. Brown and C. A Bunton, J. Chem. Soc.,
Chem. Commun., 1974, 969–971; (c) H. Ihara, S. Ono, H. Shosenji
and K. Yamada, J. Org. Chem., 1980, 45, 1623–1625; (d) R. A.
Moss, Y.-S. Lee and K. W. Alwis, J. Am. Chem. Soc., 1980, 102,
6646–6648; (e) H. Ihara, N. Kunikiyo, T. Kunimasa, M. Nango
and N. Kuroki, Chem. Lett., 1981, 667–670; (f) J. M. Brown, R. L.
Elliott, C. G. Griggs, G. Helmchen and G. Nill, Angew. Chem., Int.
Ed. Engl., 1981, 20, 890–892; (g) R. Ueoka, Y. Matsumoto,
ꢁc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
New J. Chem., 2007, 31, 86–92 | 91

View Article Online
T. Yoshino, N. Watanabe, K. Omura and Y. Murakami, Chem.
Lett., 1986, 1743–1746; (h) R. Ueoka, Y. Matsumoto, R. A. Moss,
S. Swarup, A. Sugii, K. Harada, J.-I. Kikuchi and Y. Murakami, J.
Am. Chem. Soc., 1988, 110, 1588–1595; (i) H. Ihara, K. Igata, Y.
Okubo and M. Nango, J. Chem. Soc., Chem. Commun., 1989,
1900–1902; (j) M. C. Cleji, P. Scrimin, P. Tecilla and U. Tonellato,
Langmuir, 1996, 12, 2956–2960; (k) Y. Zhan and W. Wu, Tetra-
hedron: Asymmetry, 1997, 8, 3575–3578; (l) M. J. Diego-Castro and
H. C. Hailes, Chem. Commun., 1998, 1549–1550.
2 (a) D. Tickle, A. George, K. Jennings, P. Camilleri and A. J. Kirby,
J. Chem. Soc., Perkin Trans. 2, 1998, 467–474; (b) J. K. Rugutt, E.
Billiot and I. M. Warner, Langmuir, 2000, 16, 3022–3029; (c) T. J.
M. De Bruin, A. T. M. Marcelis, H. Zuilhof, L. M. Rodenburg, H.
A. G. Niederlander, A. Koudijs, P. E. M. Overdevest, A. Van Der
Padt and E. J. R. Sudholter, Chirality, 2000, 12, 627–636.
3 (a) E. M. Arnett and J. M. Gold, J. Am. Chem. Soc., 1982, 104,
636–639; (b) J.-H. Fuhrhop, P. Schnieder, J. Rosenberg and E.
Boekema, J. Am. Chem. Soc., 1987, 109, 3387–3390; (c) S. Pathir-
ana, W. C. Neely, L. J. Myers and V. Vodyanoy, J. Am. Chem.
Soc., 1992, 114, 1404–1405; (d) J. Bella, S. Borocci and G. Mancini,
Langmuir, 1999, 15, 8025–8031; (e) D. Izhaky and L. Addadi,
Chem.–Eur. J., 2000, 6, 869–874; (f) T. Kawasaki, M. Tokuhiro, N.
Kimizuka and T. Kunitake, J. Am. Chem. Soc., 2001, 123,
6792–6800; (g) S. Lalitha, A. Sampath Kumar, K. J. Stine and
D. F. Covey, J. Supramol. Chem., 2001, 1, 53–61; (h) H. Nakaga-
wa, M. Yoshida, Y. Kobori and K.-I. Yamada, Chirality, 2003, 15,
703–708; (i) S. Borocci, F. Ceccacci, L. Galantini, G. Mancini, D.
Monti, A. Scipioni and M. Venanzi, Chirality, 2003, 15, 441–447;
(j) C. Bombelli; S. Borocci, F. Lupi, G. Mancini, L. Mannina, A.
L. Segre and S. Viel, J. Am. Chem. Soc., 2004, 126, 13354–13362;
(k) R. Andreani, C. Bombelli, S. Borocci, J. Lah, G. Mancini, P.
Mencarelli, G. Vesnaver and C. Villani, Tetrahedron: Asymmetry,
2004, 15, 987–994; (l) F. Ceccacci, G. Mancini, A. Sferrazza and C.
Villani, J. Am. Chem. Soc., 2005, 127, 13762–13763.
7 (a) P. U. Biedermann, V. Schurig and I. Agranat, Chirality, 1997,
9, 350–353; (b) F. Grein, J. Phys. Chem. A, 2002, 106, 3823–3827.
8 (a) M. J. Frisch, G. W Trucks, H. B. Schlegel, G. E. Scuseria, M.
A. Robb, J. R. Cheeseman, V. G. Zakrzewski, Jr, J. A. Montgom-
ery, R. E. Stratmann, J. C. Burant, S. Dapprich, J. M. Millam, A.
D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi, V.
Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo,
S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K.
Morokuma, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B.
Foresman, J. Cioslowski, J. V. Ortiz, A. G. Baboul, B. B. Stefanov,
G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R.
L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A.
Nanayakkara, C. Gonzalez, M. Challacombe, P. M. W. Gill, B.
Johnson, W. Chen, M. W. Wong, J. L. Andres, C. Gonzalez, M.
Head-Gordon, E. S. Replogle and J. A. Pople, GAUSSIAN 98
(Revision A.7), Gaussian, Inc., Pittsburgh PA, 1998; (b) M. J.
Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, Jr, J. A. Montgomery, T. Vreven, K. N. Kudin,
J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B.
Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H.
Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hase-
gawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M.
Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo,
J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J.
Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K.
Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G.
Zakrzewski, S. Dapprich A. D. Daniels, M. C. Strain, O. Farkas,
D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J.
V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B.
Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L.
Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A.
Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W.
Chen, M. W. Wong, C. Gonzalez and J. A. Pople, GAUSSIAN 03
(Revision B.05), Gaussian, Inc., Pittsburgh PA, 2003.
4 F. Ceccacci, G. Mancini, P. Mencarelli and C. Villani, Tetrahe-
dron: Asymmetry, 2003, 14, 3117–3122.
9 G. Schaftenaar and J. H. Noordik, J. Comput. Aided Mol. Des.,
2000, 14, 123–134.
5 C. Wolf, W. A. Konig and C. Roussel, Liebigs Ann., 1995,
781–786.
10 R. W. Stoughton and R. Adams, J. Am. Chem. Soc., 1932, 54,
4426–4434.
¨
6 F. B. Dains, A. W. Magers and W. L. Steiner, J. Am. Chem. Soc.,
1930, 52, 1570–1572.
11 A. G. Giumanini, G. Chiavari, M. M. Musini and P. Rossi,
Synthesis, 1980, 743–746.
ꢁc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
92 | New J. Chem., 2007, 31, 86–92