Unprecedented synthesis of 1,3-dimethylcyclobutadiene in the solid state and aqueous solution

Article abstract of DOI:10.1002/chem.201100693

Cyclobutadiene (CBD), the smallest cyclic hydrocarbon bearing conjugated double bonds, has long intrigued chemists because of its chemical characteristics. The question of whether the molecule could be prepared at all has been answered, but the parent compound and its unperturbed derivatives have eluded crystallographic characterization or synthesis "in water". Different approaches have been used to generate and to trap cyclobutadiene in a variety of confined environments: a) an Ar matrix at cryogenic temperatures, b) a hemicarcerand cage enabling the characterization by NMR spectroscopy in solution, and c) a crystalline guanidinium-sulfonate-calixarene G₄C matrix that is stable enough to allow photoreactions in the solid state. In the latter case, the 4,6-dimethyl-α-pyrone precursor, Me₂1, has been immobilized in a guanidinium-sulfonate-calixarene G₄C crystalline network through a combination of non-covalent interactions. UV irradiation of the crystals transforms the entrapped Me₂1 into a 4,6-dimethyl-Dewar-β-lactone intermediate, Me₂2, and rectangular-bent 1,3-dimethylcyclobutadiene, Me₂CBD^R, which are sufficiently stable under the confined conditions at 175 K to allow a conventional structure determination by X-ray diffraction. Further irradiation drives the reaction towards Me₂3&Me₂CBD ^S/CO₂ (63.7 %) and Me₂CBD^R (37.3 %) superposed crystalline architectures and the amplification of Me ₂CBD^R. The crystallographic models are supported by additional FTIR and Raman experiments in the solid state and by ¹H NMR spectroscopy and ESI mass spectrometry experiments in aqueous solution. Amazingly, the 4,6-dimethyl-Dewar-β-lactone, Me₂2, the cyclobutadiene-carboxyl zwitterion, Me₂3, and 1,3- dimethylcyclobutadiene, Me₂CBD, were obtained by ultraviolet irradiation of an aqueous solution of G₄C{Me₂1}. 1,3-Dimethylcyclobutadiene is stable in water at room temperature for several weeks and even up to 50 °C as demonstrated by ¹H NMR spectroscopy. Copyright

Full text of DOI:10.1002/chem.201100693

FULL PAPER
DOI: 10.1002/chem.201100693
Unprecedented Synthesis of 1,3-Dimethylcyclobutadiene in the Solid State
and Aqueous Solution
Yves-Marie Legrand, Arnaud Gilles, Eddy Petit, Arie van der Lee, and
Mihail Barboiu*[a]
Abstract: Cyclobutadiene (CBD), the
smallest cyclic hydrocarbon bearing
conjugated double bonds, has long in-
trigued chemists because of its chemi-
cal characteristics. The question of
whether the molecule could be pre-
pared at all has been answered, but the
parent compound and its unperturbed
derivatives have eluded crystallograph-
ic characterization or synthesis “in
water”. Different approaches have
been used to generate and to trap cy-
clobutadiene in a variety of confined
environments: a) an Ar matrix at cryo-
genic temperatures, b) a hemicarcerand
cage enabling the characterization by
NMR spectroscopy in solution, and c)
solid state. In the latter case, the 4,6-di-
methyl-a-pyrone precursor, Me21, has
been immobilized in a guanidinium–
sulfonate–calixarene G4C crystalline
network through a combination of non-
covalent interactions. UV irradiation of
the crystals transforms the entrapped
Me21 into a 4,6-dimethyl-Dewar-b-lac-
tone intermediate, Me22, and rectangu-
Me23&Me2CBDS/CO2 (63.7%) and
Me2CBDR (37.3%) superposed crystal-
line architectures and the amplification
of Me2CBDR. The crystallographic
models are supported by additional
FTIR and Raman experiments in the
solid state and by H NMR spectrosco-
py and ESI mass spectrometry experi-
ments in aqueous solution. Amazingly,
1
lar-bent
1,3-dimethylcyclobutadiene,
the
4,6-dimethyl-Dewar-b-lactone,
Me2CBDR, which are sufficiently stable
under the confined conditions at 175 K
to allow a conventional structure deter-
mination by X-ray diffraction. Further
irradiation drives the reaction towards
Me22, the cyclobutadiene-carboxyl
zwitterion, Me23, and 1,3-dimethylcy-
clobutadiene, Me2CBD, were obtained
by ultraviolet irradiation of an aqueous
solution of G4C
ACHTUNGTREN{NUGN Me21}. 1,3-Dimethyl-
AHCTUNGTRENGNcUN yclobutadiene is stable in water at
room temperature for several weeks
and even up to 508C as demonstrated
by 1H NMR spectroscopy.
Keywords: calixarene · cyclobuta-
a
crystalline guanidinium–sulfonate–
diene
· Dewar-b-lactone · host–
calixarene G4C matrix that is stable
enough to allow photoreactions in the
guest systems · X-ray diffraction
Introduction
its dimerization.[15,16] The question of whether the molecule
could be prepared at all was largely answered, but cyclobu-
tadiene and its unperturbed precursors have eluded crystal-
lographic characterization. A further successful approach is
related to the design of a crystalline host matrix that might
present: a) good quality diffraction data and b) an optimal
design of the host confining volume, dimensionally adapted
to the cyclobutadiene precursor guests and/or presenting an-
choring fixing groups. These considerations inspired us to
design an appropriate crystalline host matrix for the synthe-
sis of cyclobutadiene. The photolysis reaction of the 4,6-di-
methyl-a-pyrone precursor Me21 under confinement in a
protective guanidinium–calixarene–sulfonate G4C matrix
allows the preparation of the dimethyl-Dewar-b-lactone
Me22, the 1,3-cyclobutadiene-carboxyl zwitterion intermedi-
ate Me23, as well as1,3-dimethylcyclobutadiene, Me2CBD, in
the solid crystalline state and in aqueous solution
(Scheme 1).[17,18] We report here a more detailed analysis of
the formation of Me2CBD in the solid state, based on more
advanced refinements of the original X-ray data and on new
supporting FTIR, Raman, and NMR spectroscopic, and ESI
mass spectrometric data. 1,3-Dimethylcyclobutadiene is
stable in water in the presence of the G4C matrix at room
The chemistry of cyclobutadiene (CBD)[1–8] and the corre-
sponding theoretical calculations[9–14] have been the object of
significant research effort. Crucial experiments leading to
trapping cyclobutadiene and to understanding its properties
and to elucidating its structure have provided a number of
highlights over the last 40 years. The Ar matrix isolation of
cyclobutadiene by Corey,[1] Chapmann,[2] Krantz,[3,4]
Maier,[5–7] Michl[8] and their respective co-workers are non-
exclusive examples of the fascinating facets of cyclobuta-
diene chemistry.[5–7] In a seminal experiment Cram and co-
workers succeeded in isolating cyclobutadiene by sequester-
ing it in a hemicarcerand cage in solution, thereby inhibiting
[a] Dr. Y.-M. Legrand, Dr. A. Gilles, E. Petit, Dr. A. van der Lee,
Dr. M. Barboiu
Adaptive Supramolecular Nanosystems Group
Institut Europꢀen des Membranes
ENSCM-UMII-UMR-CNRS5635
Place Eugꢁne Bataillon CC047
34095 Montpellier Cedex 5 (France)
E-mail: mihai.barboiu@iemm.univ-montp2.fr
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100693.
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Importantly, during the irradiation of G4CACTHNUTRGNEG{NU Me21}, the G4C
matrix remains unchanged (Figure 2a), whereas the struc-
ture of confined Me21 is modified during the series of irradi-
ations (Figure 2b). Such irradiation procedures (2ꢃ10 min)
induce the conversion of G4CACTHUNGRTNE{NUG Me21} into the
G4C{Me21&Me22&Me2CBDR} architecture (Figure 3). The
cigar-shaped ellipsoid for atom C3 led us to use a two-way
split model for C3, consistent with the co-existence of a dis-
torted Me21 geometry and the ꢄbutterflyꢀ-type geometry of
Me22 (Figure 3).[14] Supplementary separate density maxima
on the electronic density map were detected on both sides
of Me22, corresponding to 22.7% conversion of Me22 to
Me2CBDR. They remain stable after the splitting model was
applied (Figure 3).
The Me2CBDR ring shows a relaxed rectangular-bent ge-
ometry, asymmetrically distorted, its plane being slightly
flipped with the methyl groups lying out-of-plane with simi-
lar bond lengths and angles as predicted by theory[22,23] and
experiments for the ground state of Me2CBDR.[24–26] Further
irradiation (60 min) led to the transformation of both Me21
and Me22 into superposed Me23&Me2CBDS/CO2 structures
Scheme 1. Electrocyclic rearrangement under confined conditions in
aqueous solution of a-pyrone Me21 leads to 4,6-dimethyl-Dewar-b-lac-
tone, Me22; photo-fragmentation of Me22 occurs via the 1,3-cyclobuta-
diene-carboxylate zwitterion Me23 or Me2CBDS/CO2 complex, which, by
eliminating CO2, leads to 1,3-dimethylcyclobutadiene, Me2CBDR. Finally,
conversion of Me2CBDR leads to its dimers Me24 and Me24’.
temperature for several weeks
and even up to 508C during
the NMR measurements.
Results and Discussion
Solid-state photosynthesis of
CBD in a crystalline matrix
under confined conditions: In-
Figure 1. Crystal structures of the G4C host matrix and of the G4CACHTNUTRGNEUNG
{Me21} host–guest complex.[17]
clusion
of
4,6-dimethyl-a-
pyrone, Me21, within the G4C
matrix[17–19] in an aqueous solu-
tion of either G4C/Me21 or 4·G/
C/Me21 components led to
single crystals of G4CACTHNUTRGEN{UNG Me21}
(Figure 1).
The structural contributions
of G to the G4C{Me21} architec-
ACHTUNGTRENNUNG
ture are: a) stabilization
through hydrogen bonding of
the cone conformation of the
calixarene C, in which the 4-Me
group of Me21 is fixed through
three CH–p interactions;[20] b)
sandwiching of the fully local-
ized canonical form[21] of Me21
between two G groups while c)
the carbonyl oxygen atom of
Me21 points outward, forming
anchoring hydrogen bonds with
a third quasi-coplanar G cation
(Figure 1) (see the Supporting
Information for details).[17]
Figure 2. X-ray crystallographic representation of the Me2CBD formation pathway from photolysis of Me21: a)
Views of the initial (red line) and irradiated (blue line) single-crystal X-ray structures, illustrating the stability
of the G4C crystalline matrix including the superposed Me21 (cyclamen), Me22, or Me23&Me2CBDS/CO2 com-
plex (blue) and Me2CBDR (orange) photo-products (ball-and-stick); b) crystal structure in stick representation
of the G4C
ACHTUTGNERN{NGU Me21} complex, which by UV irradiation transforms progressively into the G4CACHTUGNTRENN{UNG Me22} and G4C-
AHCTUNGTRENNUNG
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1,3-Dimethylcyclobutadiene
FULL PAPER
inspection of the crystal pack-
ing of G4CACTHNUGTRNEU{GN Me22} reveals an up-
down arrangement of C mole-
cules in the cone conforma-
tion[27] that affords free space
defined by the internal pocket
of component C, available to
guest molecules during the as-
sembly of the crystal lattice.
(Figure 4). In the crystal lattice
the bilayer arrangement is con-
solidated by strong hydrogen
bonds between four G1–G4 cat-
ions and eight sulfonate moiet-
ies of two C molecules.[28] The
Me22 molecule is sandwiched
between two G5, G6 cations,
whereas the carbonyl oxygen
atom of Me22 points outward,
forming anchoring hydrogen
bonds with a third quasi-copla-
nar G7 cation. A last G8 cation
is positioned between two
neighboring C molecules of the
same layer and is perpendicu-
larly oriented to the confined
guest molecule (Figure 4). This
generates completely closed
cavities in the solid state, in
which the guest molecules are
properly confined through
a
combination of noncovalent in-
teractions. Under such confined
conditions the formation of
zwitterion Me23[29] is more in
ꢀ
line with the observed C2 C3
ꢀ
and C6 O1 distances and
seems reasonable since the host
matrix is ionic/polar (see the
Supporting Information for de-
tails). The square geometry of
Figure 3. X-ray crystallographic superposed models of the photolysis reaction of 4,6-dimethyl-a-pyrone, Me21.
Structures are shown for Me21, leading after irradiation for 25 min to the Dewar-b-lactone Me22 (77.3%) and
the rectangular-bent Me2CBDR (22.7%) and then after irradiation for 60 min to the Me23&Me2CBDS/CO2
(62.7%) and the rectangular-bent Me2CBDR (37.3%) (see text and Supporting Information for the two-way
splitting models).
ꢀ
the C3 C6 ring is more in line
with that of the Me2CBDS/CO2
complex. These results are simi-
lar to the previous theoretical
and the amplification of Me2CBDR. Considering the elec-
tron density map of G4C{ Me23&Me2CBDS/CO2
&Me2CBDR}, which can be connected in a reasonable
manner, we may argue that the crystal structure is not really
associated with a local disorder (Figure 3). We observe two
significant tendencies when Me22 transforms into
calculations on energy minima corresponding to distances of
1.6–1.8 ꢅ for the CBD/CO2 complex.[9] Moreover, a curious
inhibition of the decomposition of the CBD has been ob-
served experimentally in the presence of CO2 in the Ar
matrix.[8] The most realistic model of the transition-state ar-
chitecture resulting from the photolysis of Me22 toward
Me2CBDR involves the superposed structures Me23 and
Me2CBDS/CO2 being present in the G4C host matrix. The
Me2CBDR rectangular geometry is quantitatively amplified
(22.7%!37.3%) after the last irradiation step (Figure 2b).
The crystallographic results show that the elimination of
CO2 induces a 908 rotation of the Me2CBDR molecule rela-
S
R
ꢀ
Me23&Me2CBD /CO2 toward Me2CBD : 1) the C2 C3 and
ꢀ
C6 O1 bonds expand and 2) the C3-C4-C5-C6 ring with a
trapezoidal form in Me22 tends toward a square geometry in
Me2CBDS (see the Supporting Information and Figure S1
for details). Owing to a cage and hydrogen-bonding effects,
the CO2 fragment remains close to CBD (Figure 4). Close
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M. Barboiu et al.
IR spectra shows that the carbonyl vibration bands at 1710
and 1557 cmꢀ1 strongly decrease in intensity at the same
rate with irradiation time, whereas a new CO2-asymmetric
stretching vibration of the CO2 band at 2333 cmꢀ1 increas-
es.[30] This corresponds to the progressive conversion of the
lactone-type compounds Me21 and Me22 to Me2CBDR and
CO2. Krantz et al.[4] assumed a face-to-face interaction be-
tween CBD and the bent molecule CO2. Our results show
that the interaction between CO2 and the CBD under con-
finement is manifested by a shift of about 17 cmꢀ1 from the
position of the free gaseous CO2 asymmetric fundamental
band at 2350 cmꢀ1.[30]
The absence of the symmetric stretching vibration of the
free gaseous CO2 band at 2360 cmꢀ1 also shows that the CO2
is asymmetrically sequestered through hydrogen-bonding
and intermolecular interactions with the CBD within the
G4C host matrix. Moreover, the absence of these bands in
the spectra of the G4CACHTNURTGENN{UG Me21} and G4CCAHTUNGTREN{NGUN Me22} host–guest sys-
tems is clearly the result of CO2 development and not be-
cause of its simple absorption from air. These IR data leave
no doubt that the CO2 molecule can be considered as a dis-
crete entity during the photochemical process (l=320–
500 nm at 175 K). Further irradiation with higher energy
light, l=190–500 nm, does not lead to an important increase
of the intensity of the CO2 vibration band (see Figure 5).
The crystallographic results show that Me2CBDR can be
unequivocally identified during the last irradiation step at a
maximum conversion of 37.4% in the presence of the Me23
and Me2CBDS/CO2 species. It is known that the Dewar-b-
lactone intermediate gives rise to CO2 and CBD when irra-
diated with light of higher energy (l<290 nm).[2] It has been
shown that the same irradiation energy is also unfavorable
for completion of the reaction, since the concentration of
CBD rises to a maximum and then decreases as irradiation
Figure 4. Crystal packing of the G4CACHTNUTRGNENUG{Me22} calixarene bilayers that con-
fine the Me22 (space-filling representation), and the confined fragmenta-
tion of Me22 to give Me2CBDR.
ꢀ
tive to C3-C4-C5-C6 ring of Me22 (Figure 3). The -C H
atoms of the cyclobutadiene rings are strongly H-bonded
(dOꢀ = 2.83–2.93 ꢅ) to sulfonate groups, orienting the
H
Me2CBDR and Me2CBDS along the orthogonal diagonals de-
termined by the sulfonate rims.[18c]
The CO2 moiety of Me22 presents a restricted degree of
relative mobility within the host system. A rotational
motion toward the G7 moiety might be possible, considering
the overall interactions of the CO2 moiety with the superior/
lateral limit of the crystalline matrix. Moreover, one might
argue that the CO2 fragment could not be in such a vicinity
with Me2CBDR and therefore is
is continued, yielding acetylene and ACTHNUTRGNEUNG
(CBD)2.[2] Unfortunate-
ly, only very poor crystals could be obtained by using a
high-energy light source (l=190–500 at 175 K) and only low
intensity data could be collected. The quality of the X-ray
diffraction data can only be maintained if the initial irradia-
not present in the elementary
cells where Me2CBDR is pres-
ent (see Supporting Informa-
tion for details)
IR and Raman spectroscopic
studies in the solid state: To
shed more light on the mecha-
nisms involved in the elimina-
tion and the interaction of the
CO2 moiety with cyclobuta-
diene in confined conditions,
we
have
performed
IR
(Figure 5) and Raman studies
(see Figure S2 in the Support-
ing Information) on crystalline
Figure 5. FTIR spectra showing the effect of the irradiation of crystals of G4CACTHNUTRGENUGN{Me21} (black line) at l=320–
samples. Close inspection of the 500 nm (t=10, 20, 60 min.) and at l=190–500 nm (t=70 min).
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1,3-Dimethylcyclobutadiene
FULL PAPER
tion conditions are used: l=320–500 nm. Moreover the
same experiments on the guest matrix G4C crystals preserve
good crystallinity in the absence of the guest molecules. We
think that the low-quality X-ray data are related with the
critical amount of gaseous CO2 developed together with the
loss of some of the water molecules induced by local heating
during the irradiation. This undermines the matrix integrity
and the reaction cannot be completed to isolate Me2CBDR
as a unique compound in the cavity.
system previously observed in the solid state: the 4-Me
group of Me21 is hydrophobically confined within the calix-
arene pocket (see the Supporting Information for details).
This assumption was confirmed by the amplified shielding of
the Me4 hydrogens, by increasing the concentration of the
host–guest complex G4CACTHNUTRGNEUNG
{Me21} to 2.5ꢃ10ꢀ2 molLꢀ1, and by
lowering the temperature from 258C to 78C (see Figure S4
in the Supporting Information).
Synthesis of Me2CBD in aque-
ous solution under confined
conditions: Following these
solid-state
studies,
the
G4C{Me23&Me2CBDS/CO2
&Me2CBDR} crystals obtained
after the last irradiation step
were dissolved in D2O and the
1H NMR spectrum was record-
ed. The spectrum shows a series
of peaks in a 3:1 ratio, at d=
1.85–1.94 ppm
5.89 ppm,
and
respectively,
d=
in
accord with experimental[16] and
theoretical[31] reported values
for CBD (Figure 6a). The mass
spectra recorded in D2O solu-
tions show the correct molecu-
lar mass of Me2CBD: positive-
field ionization M–D+ m/z 82
(Figure 6b) and negative-field
ionization, M–Hꢀ: m/z 79 (Fig-
ure 6c). These measurements
are consistent with the major
presence of Me2CBD in aque-
ous solution, together with
other discrete species, which
present minor signals.
In general, low-polar organic
molecules such as Me21 or
Me2CBD repel water mole-
cules.[32] A special effect can be
obtained if molecules with a hy-
drophilic external hypersurface
are available to bind nonpolar
substrates in their hydrophobic
cavities in solution in water.[33]
This is the case for Me21, which
can be solubilized in water in
the presence of the G4C host
matrix as the result of the con-
finement of the Me21 guest
within the calixarene pocket.
1
The H NMR spectrum of G4C-
ACHTUNGTRENNUNG
Figure 6. a) 300 MHz 1H NMR spectra at 258C, b) positive and c) negative electrospray ionization mass spec-
tra of a 2ꢃ10ꢀ4 molLꢀ1 D2O solution obtained by dissolving the irradiated crystals of G4C
ACTHNUGTRENNG{U Me21} at l=320–
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M. Barboiu et al.
3:1 ratio, at d=1.74 ppm and
d=5.78 ppm, respectively (Fig-
ure 7a, third spectrum). This
spectrum is very similar with
the 1H NMR spectrum of dis-
solved crystals of G4CACTHNUTRGNEG{NU Me21} ir-
radiated at l=320–500 nm for
60 min (Figure 6a), and is con-
sistent with the presence of
Me2CBD. As no further appar-
ent alteration in the species dis-
tribution was observed on sup-
plementary irradiations at l=
320–500 nm, further irradiation
with higher energy light, l=
190–500 nm (Figure 7a, third
and fourth spectra), led to the
progressive
conversion
of
Me2CBD to its dimers Me44
and Me44’, yielding a series of
two new sets of resonances in
an approximately 3:1 ratio at
d=1.98 to 2.15 and; d=5.0 to
5.12, respectively.
Having observed important
concentration and temperature
effects on encapsulation of the
Me21 guest in the G4C host
matrix (see Figure S4 in the
Supporting Information for de-
tails), we decided to perform
the same set of experiments on
a
more concentrated (2.5ꢃ
10ꢀ3 molLꢀ1) D2O solution of
G4C
{Me21}
at
78C.
The
500 nm for 10 and 25 min are
consistent with the presence of
Me22, with signals at d=2.75
(H3) and 4.80 ppm (H5) and
d=1.48 (Me6) and ꢀ0.3 ppm
(Me4) in slow exchange with
the carboxyl zwitterions, and
Me23 (Figure 7b), with sharp
signals at d=3.08 (H3) and
5.62 ppm (H5) and d=1.38
(Me6) and 1.03 ppm (Me4) (Fig-
1
Figure 7. 300 MHz H NMR spectra of the a) 4.6ꢃ10ꢀ3 molLꢀ1 and b) 2.5ꢃ10ꢀ2 molLꢀ1 D2O solutions of G4C-
{Me21} at 78C for different irradiation times at l=320–500 nm or at l=190–500 nm; c) 300 MHz 1H NMR
spectra of the 2.5ꢃ10ꢀ2 molLꢀ1 D2O solution of G4C
{Me2CBD} at various temperatures.
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ure 7b, second and third spec-
Next, the irradiation of a diluted solution of G4C
{Me21} in
tra). These results were confirmed by electrospray mass
spectrometry. After the first two irradiation steps at l=320–
500 nm the initial positive-field ionization of Me22G+ at m/z
D2O (4.6ꢃ10ꢀ3 molLꢀ1) for 10 min at l=320–500 nm gave a
1
very complex but sharp H NMR spectrum, indicative of the
presence of several discrete species in solution, including
the initial Me21 compound (Figure 7a, second spectrum).
After a second irradiation period (30 min) at l=320–
500 nm, a dramatic simplification of the H NMR spectrum
is observed, yielding a series of peaks in an approximately
184 strongly decreases in intensity, whereas a new
Me23GD2O+ signal at m/z 204 increases (see Figure S6 in
the Supporting Information). Similarly, the initial negative-
field ionizations for CMe214ꢀ at m/z 216 and CGMe213ꢀ at
m/z 308 decrease in intensity at the expense of the signals
1
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1,3-Dimethylcyclobutadiene
FULL PAPER
for CMe23D2O4ꢀ at m/z 220 and CGMe23D2O3ꢀ at m/z 314
(see Figure S7 and S8 in the Supporting Information). These
results are consistent with the progressive formation of
polar hydrated guest species in the cavity such as Me23*D2O
hydrated zwitterions, which seem to be more persistent than
low-polar Me22, since the host matrix is ionic/polar. Further
irradiations at l=320–500 nm led to the progressive conver-
sion of Me22 and Me23 and the spectrum is consistent with
the presence of major amounts of encapsulated Me2CBD,
which displays exchange-broadened signals at d=5.20
(H3,H5) and d=1.12 (Me6) and 0.67 (Me4), and minor
amounts of the dimers Me44 and Me44’ (Figure 7b, fourth,
fifth spectra). Importantly, the 1H NMR peaks for the
methyl hydrogens of Me2CBD are indicative of methyl
groups located in two different magnetic environments (Fig-
ure 7b, c). These data demonstrate that high concentrations
and lower temperatures increase the stability of G4C-
um G4C matrix at lower energetic conditions in the solid
crystalline state and in aqueous solution. This is important
in the context of efforts by organic chemists to trap cyclobu-
tadiene, to understand its properties, and to elucidate its
structure.[1–14] However, 4,6-dimethyl-a-pyrone, Me21, the di-
methyl-Dewar-b-lactone Me22, and 1,3-dimethylcyclobuta-
diene, Me2CBD, have eluded X-ray structural characteriza-
tion. Our present attempts to isolate the dimethyl-Dewar-b-
lactone Me22 and 1,3-dimethylcyclobutadiene in a confined
protective crystalline matrix furnish their crystal structures.
The geometry of Me22 is amazingly similar in terms of its
bond lengths and angles to that of the Dewar-b-lactone mol-
ecule predicted by theory.[12,14] The crystallographic results
show that the elimination of the CO2 induces a 908 rotation
of the Me2CBDR molecule relative to C3-C4-C5-C6 ring of
Me22. The intermediate structure resulting from the photol-
ysis of Me22 toward Me2CBDR corresponds to a superposi-
tion of the Me23 and Me2CBDS/CO2 structures in the G4C
host matrix. These crystallographic structures are supported
by additional FTIR, Raman, and NMR spectroscopic data,
and ESI mass spectrometric data from experiments on the
photolysis reaction of Me21 in the solid state and in aqueous
solution.
Generations of chemists have considered water for carry-
ing out biological reactions, and only in the last two decades
have they shed light on its use as a media to explore the hy-
drophobic effects in organic reactions.[32–34] These considera-
tions inspired us to design unprecedented experiments in
which the G4C system was used as a host protective matrix
for the synthesis of Me2CBD in aqueous solution. Previous
or very recent results showed that cyclobutadiene,[25] cyclo-
butadieneiron-tricarbonyl,[35] or tetrasilacyclobutadiene[36]
can be stabilized within a highly protective hydrophobic en-
vironment of bulky hydrocarboneous substituents, allowing
crystallographic characterization. Herein, of very special in-
terest is the stability of the parent Me2CBD and its unper-
turbed precursors Me22 and Me23 under protection of the
G4C matrix. Moreover, the Me2CBD remains stable for sev-
eral weeks at room temperature and even at 508C in aque-
ous solution. This opens a new perspective for understand-
ing the complex effects that influence the stability of
Me2CBD in aqueous solution. Further research is needed to
fully determine the role that water plays in this stabilization
and how the protective calixarene-guanidinium G4C matrix
stabilizes such reactive intermediates and products.
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
was performed. The two peaks corresponding to Me2CBD
1
at 278 K converge to give a shielded sharp H NMR signal
at d=2.02 upon heating at 323 K. This suggests that
Me2CBD interconverts rapidly in the calixarene cavity
below the coalescence temperature at 313 K (Figure 7c).
The H3 and H5 protons initially at d=5.30 ppm converge to
1
give a shielded sharp H NMR signal at d=6.2 ppm in D2O.
Two levels of diffusion rates were revealed by the NMR
DOSY experiments measured under the same conditions
(see Figure S5 in the Supporting Information). The G4C
matrix presents a diffusion coefficient of 2.0ꢃ10ꢀ10 m2 sꢀ1
which is smaller than that of the Me2CBD molecule (3.4ꢃ
10ꢀ10 m2 sꢀ1) (see Table S1 in the Supporting Information).
This indicates that the interconversion process occurs by a
releasing process of the Me2CBD by the cavity of the calix-
arene in aqueous solution.
The last point we addressed in this study was related to
the reversibility of the reaction between CBD and CO2,
which yields Me22 or Me23. All previous studies agree that
the CO2/CBD interaction results “from the repulsion be-
tween CBD and CO2 rather than an attraction”[4] and is
mostly favored by the solid matrix constraints/effects.[1–18]
1
Within this context, the H NMR spectra of G4C
N
showed no further evolution after the saturation of the
aqueous solution with gaseous CO2. These NMR results
have been also confirmed by Raman spectroscopy investiga-
tions in aqueous solution (see Figure S3 in the Supporting
Information for details).
Experimental Section
All the compounds were purchased from Aldrich and used without pu-
rification. 1H NMR spectra were recorded on an ARX 300 MHz in D2O
with the use of the residual solvent peak as reference. The assignments
were made on the basis of COSY and NOESY spectra. Mass spectromet-
ric studies (508C, cone voltage of Vc =5 V) were performed by using a
QuatroMicro triple Quad, Waters apparatus. Samples were introduced di-
rectly with a syringe. In situ IR and Raman studies were performed
under liquid nitrogen flow or at room temperature by using a Nicolet 710
Apparatus from Thermo Fisher and a Globar Source, DTGS detector, re-
Conclusion
The present results show that the photolysis reaction of 4,6-
dimethyl-a-pyrone, Me21, leads to the formation of the di-
methyl-Dewar-b-lactone Me22, the carboxyl zwitterion
Me23, and 1,3-dimethylcyclobutadiene, Me2CBD, under hy-
drophobic confinement in a protective calixarene-guanidini-
Chem. Eur. J. 2011, 17, 10021 – 10028
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10027

M. Barboiu et al.
spectively, resolution: 4.32 scans and a Labram 1B Confocal from Jobin–
Yvon, Ar/Kr Laser 647.1 nm, power 100 mW, detector CCD30–11
1024*256 pixels, pixel size 26 mm2, picture area 26.6ꢃ6.7 mm. Optics 50
(numerical opening=0.5), 100 (numerical opening=0.95), Labspec 5 ac-
quisition and treatment software.
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Received: March 5, 2011
Published online: August 4, 2011
10028
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ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 10021 – 10028