8
c
ratio, whereas a 1:1 stoichiometry was established for all other
complexes 7b (4b:3), 8a–b (5a–b:3) and 9a–b (6a–b:3). We assumed
that the lipophilic cycle stood inside the cavity and that the ketone
function was localized on the upper part of the macrocycle, in the
more hydrophilic area (ref. 6 and ref. therein). Therefore, 3 could
be submitted to an important steric constraint, but its reactive site
could be still accessible to envisage an organic reaction.
molecules engulfed in the cavity. Surprisingly, our structural data
present the same parameters as those described by Saenger and
8c
coworkers despite the important volume difference between the
guests. Indeed, the superimposition of these structures revealed
identical features in terms of macrocycle conformations and crystal
packings. Regarding the inclusion geometry, 10a is engulfed in
the macrocycle and only the cyanobenzyle group protrudes from
the cavity (Fig. 1). Although thermal displacement ellipsoids of the
guest are rather large at room temperature, this relative orientation
of host and guest components was confirmed by a structural
analysis performed at 100 K, leading to identical atomic positions
with smaller ellipsoids. From this structure, it appears that the E
geometry of the diene cannot be tolerated with such an inclusion,
and the ketone function is hidden behind the methoxy functions of
the macrocycle 6b. As the synthesis occurs in the solid state, this
new inclusion geometry can be postulated as the real reaction
intermediate, without considering packing features (grinding of the
reagent powders was necessary before MW irradiation).
Consequently, this new position prevents the second aldolisation
reaction. The MW irradiation might therefore eject 10a from 11 or
To avoid side mechanisms, the reaction conditions have been
chosen in order to fulfil two conditions: i. Presence of water should
be avoided due to the reversible aldol condensation; ii. Organic
solvent are well-known to shift the host–guest equilibrium in Cd
chemistry, and are not suitable to preserve the stereospecific
constraints. Therefore, the condensation was carried out without
7
solvent under microwave (MW) irradiation. The reaction was first
optimized in heterogeneous phase with 3 (liquid) and 2 (solid)
and catalyzed under various MW irradiation conditions. The
(E,E)-isomer 1c was obtained with 74% yield after simple
filtrations and washings. These conditions were applied to the
supramolecular complexes, but no reaction occurred, probably due
to the solid/solid medium. Harder conditions with 0.4 equivalent of
p-toluenesulfonic acid (PTSA) at 100 W for 20 minutes allowed the
3
from 7a–b, 8a–b and 9a, releasing the guest and then allowing the
1
reaction (Scheme 1). H NMR Analysis of reacting mixtures
condensation, followed by the reversible loss of water without
9
steric constraint in E configuration. The MW irradiation impact
revealed the disappearance of supramolecular interactions.
Formation of 1c was observed in all cases except with 6b for
which selectively 1a was obtained with 72% isolated yield. No
degradation reactions of 4a–b, 5a–b, 6a–b were detected and 6b
was totally recovered by flash chromatography. In order to
understand the underlying mechanism, the inclusion ability of the
monosubstituted product was investigated. Thus, following a
similar procedure, the monocondensation of 2 in the presence of
on the decomplexation process was studied unsuccessfully by:
NMR spectrometry (partial miscibility of 3 in water); XRPD
(
amorphisation of the reacting powders); IR spectrometry (no
significant shift). The absence of selectivity observed with 9a was
probably due to its lower molecular flexibility resulting from
intramolecular hydrogen-bonding. It can be postulated that the
combination of energetic constraints and steric effects in the
presence of activating reagent for the aldolisation reaction could be
at the origin of the decomplexation process.
9b led to a mixture of (Z)-CBCH 10a and (E)-CBCH 10b in a ratio
95:5 (Z/E) with 57% yield (Scheme 2).{
Compound 10a appears engulfed into 6b forming a new
inclusion complex 11. No complex was observed when this
reaction was carried out with 7a–b, 8a–b, and 9a; in these cases,
only the E isomer and the free macrocycles 4a–b, 5a–b, and 6a
were detected.
In conclusion, a selective, efficient, and fast access to
(
Z,E)-BCBCH 1a is reported using a solid/solid aldolisation–
crotonisation reaction on a supramolecular complex under MW
irradiation. The mechanism was elucidated by X-Ray analysis of
the intermediate complex structure 11. Thus, the target (Z,E)-2,7-
bis(4-amidinobenzylidene)cycloheptan-1-one (BABCH) can be
obtained with a superior pathway than reported in the literature
Structural investigation on a single crystal of complex 11 was
attempted,{ allowing the first structure determination of an
inclusion complex formed between an organic molecule and 6b.
In the literature, few structural data with 6b are available,
corresponding only to different hydrated forms. Among the
known structures, two of them exhibit an identical and unusual
conformation of the crown with an elliptically bowl-shaped
(
4%) from (Z,E)-2,7-bis(4-cyanobenzylidene)cycloheptan-1-one 1a
with a global yield of 21%. Work is in progress to develop a new
8a,b
structure.
In the third one, 6b is almost circular with 4.5 water
Scheme 2 Synthesis of (Z)-CBCH 10a by monocondensation of
-cyanobenzaldehyde 2 on complex 9b: formation of complex 11.
Fig. 1 Profile view of (cPM-Cd 6b/(Z)-CBCH 10a) complex 11 from
crystal structure analysis.{
4
4
008 | Chem. Commun., 2005, 4007–4009
This journal is ß The Royal Society of Chemistry 2005
Grandeury, Arnaud
