Macrocyclic Tetraimines: Synthesis and Reversible Uptake of Diethyl Phthalate by a Porous Macrocycle

Article abstract of DOI:10.1021/acs.joc.6b00768

The imine bond has attracted much attention for the synthesis of macrocycles used to construct porous materials. In the present article, we report on the synthesis of two series of isomeric macrocyclic tetraimines based on bis-alkynylbenzene diamines. Und

Full text of DOI:10.1021/acs.joc.6b00768

Article
pubs.acs.org/joc
Macrocyclic Tetraimines: Synthesis and Reversible Uptake of Diethyl
Phthalate by a Porous Macrocycle
†
‡,§
Carlos Lop
́
ez, Pablo Ballester, Carmen Rotger,†
†
‡,§
Elena Sanna, Eduardo C. Escudero-Adan
́
,
,†
and Antonio Costa*
†
Department of Chemistry, Universitat de les Illes Balears, 07122 Palma, Spain
‡
Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, Avda. Països Catalans 16,
4
3007 Tarragona, Spain
§
Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Spain
*
S Supporting Information
ABSTRACT: The imine bond has attracted much attention for the synthesis of
macrocycles used to construct porous materials. In the present article, we report on
the synthesis of two series of isomeric macrocyclic tetraimines based on bis-
alkynylbenzene diamines. Under heterogeneous solid−liquid conditions the
condensation of the diamines with isophthalaldehyde or terephthaldehyde afforded
mainly the corresponding [2 + 2] adducts. Among the eight macrocycles studied,
only the macrocycle 1 has a porous structure. The article describes not only the
synthesis of these macrocycles but also the encountered difficulties during their
preparation. Finally, we expand the use of 1a as a porous solid support by studying
its reversible and preferential liquid−solid adsorption properties for diethyl
phthalate in front of other commercial phthalates.
INTRODUCTION
molecules included in the pores of the solid material. The
■
solvent evacuation is critical to the success of the synthetic
method since the resulting apohost is prone to collapse forming
Designed materials featuring permanent porosity have interest
owing to their potential for applications in industrial chemistry,
material science, and sustainable energy. Among them, the
8
1
a denser and less porous crystal lattice.
In general, POMs are implied in situations where molecules
in the gas state diffuse trough the solid. However, the
adsorption of molecules in the liquid state at ambient
temperature is becoming increasingly relevant. For example,
recently, Davis et al. described a set of extrinsic POMs based on
steroidal ureas that adsorb a variety of aromatic guest molecules
large family of porous organic materials is of increasing
importance. This group of materials comprises severa2l
categories including metal−organic frameworks (MOFs),
3
covalent organic frameworks (COFs) and porous organic
4
polymers (POPs). All the above materials give infinitely
extended tridimensional structures containing voids or channels
used for adsorption-based applications.
A less known subset of organic nanoporous materials are
porous organic materials (POMs). POMs are crystalline or
amorphous materials based on discrete molecules held together
9
in the liquid state. Another interesting example of selective
liquid adsorption by POMs was reported by Shimizu and co-
10
workers. The authors demonstrated that intrinsic POMs
based on bis-urea macrocycles showed a preferential adsorption
of a variety of liquid polar guests. To preserve porosity, these
materials took advantage of the establishment CO···HN
hydrogen bonding interactions between urea groups located in
adjacent macrocyclic units.
5
by weak intermolecular forces. They differ from MOFs, COFs,
and POPs because the molecular-scale porosity of the solid
does not derive from infinitely extended one-, two- or three-
dimensional structures. In general, POMs are synthesized
following two main approaches. One is based on the use of
molecular units unable to pack efficiently in the solid state,
leading to molecular solids with voids suitable for gas sorption
extrinsic porous materials). The other is based on the solid-
state self-assembly of constitutive molecular units featuring
permanent inner cavities forming well-ordered pores (intrinsic
porous materials). Examples of solid materials having both
Imine-based molecular structures are common in the
synthesis of POM materials. The reversible nature of the
covalent imine bond allows the correction of covalent
connection mistakes during the synthesis, therefore providing
the prevalent formation of the thermodynamically more stable
6
(
11
structures in solution. In this vein, Cooper, Mastalerz and co-
workers demonstrated the use of the imine functionality for the
7
extrinsic and intrinsic pores are also known. In cases where
POMs are prepared by a solvent-based synthesis, the
emergence of nanoporosity requires the removal of the solvent
Received: April 7, 2016
©
XXXX American Chemical Society
A
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12
construction of POM materials. Also, Zhang and co-workers
used imine metathesis to synthesize shape-persistent imine
Chart 1
1
3
macrocycles. Within the realm of imine-based POMs, recently
we reported the macrocyclic tetraimine 1, affording unprece-
dented POMs. The solid-state self-assembly of 1 generated a
porous material 1a grounded on the “Gulliver Principle”, that is,
the stabilization of one-dimensional pore channels originated
by multiple and weak CH dispersive interactions acting
14
synergically (Figure 1).
bis-propargylic diamines 2 to 5 with terephthalaldehyde or
isophthalaldehyde. We expected that the 1,1-cyclohexane
substituents present in diamines 4 and 5 would improve the
solubility of the resulting macrocycles in less polar solvents, and
at the same time, they would promote the establishment of
multiple dispersive contacts among adjacent macrocycles in the
solid state. The diamines 2 to 5 were prepared by Sonogashira
cross-coupling of 1,3- or 1,4-diiodo benzene with propargyl
amines under “on water” conditions as previously reported by
Figure 1. (a) Line drawing structure (left) and space-filling X-ray
structures of 1a. (b) Side and top views of the spatial arrangement of
three consecutive macrocyclic units of 1 as observed in the packing of
POM 1a (CCDC 1012398).
17
us.
First, to evaluate the imine formation, we reacted
benzaldehyde (B) with diamines 4 and 5 in separated reaction
flasks. These reactions proceeded uneventfully and afforded the
bis-imines 6 and 7 in 61 and 72% yields, respectively (Scheme
We demonstrated the use of POM 1a as solid support
enabling the X-ray structure determination of included liquid
guests. This strategy is reminiscent to the crystalline sponge
1
).
Compounds 6 and 7 exhibited unique and sharp H NMR
1
1
5
method of Fujita.
signals that were indicative of their existence as a single
stereoisomer in solution. Remarkably, the diagnostic imine
protons of 6 and 7 appear at 8.84 and 8.86 ppm, respectively.
These values are ca. 0.5 ppm deshielded compared to standard
aromatic imines (see, Figure 3, for comparison), indicating the
strong influence of the triple bond magnetic anisotropy and
orientation. Single crystals of the bis-imine 7 were grown in
chloroform and analyzed by X-ray diffraction. The X-ray
structure of 7 is dictated by Y-shaped and parallel-displaced
Our search for new macrocyclic units akin to 1 led us to
consider the synthesis of other isomeric macrocyclic tetraimines
featuring rectangle-shaped cavities with molecular dimensions
close to 12 × 8 Å (Figure 1b). We hypothesized that the solid-
state self-assembly of macrocycles featuring structures and
functionalities closely related to 1 should provide POMs mainly
16
based on intra- and interdispersive interactions.
Herein, we report our findings on the macrocyclization
reaction between four 1,3- and 1,4-phenylene bis-propargylic
diamine monomers 2−5 and either, terephthalaldehyde (T) or
isophthalaldehyde (I) (Chart 1). The condensation reaction of
diamines 2−5 with terephthalaldehyde or isophthalaldehyde
could, in principle, provide eight [2 + 2] macrocycles. We have
studied the outcome of the eight possible combinations.
However, despite all the condensations were viable only the
macrocyclic tetraimine 1 exhibits a porous structure in the solid
state, 1a. To further demonstrate the use of 1a as porous
support, we investigated the selective liquid−solid uptake of
diethyl phthalate over other phthalates.
18
aromatic interactions and confirmed the anti configuration of
the imine bonds (Supporting Information).
To minimize undesired polymerization side reactions, the
condensations leading to 1 and the macrocycles 8−14 were
performed on relatively diluted EtOAc solutions (<10− M)
containing equimolar amounts of the corresponding diamines
2
19
and dialdehydes at room temperature. In all cases, upon
standing for evolution, we observed the formation of a
precipitate after a period ranging from one to 8 weeks since
the start of the reaction.
The analysis of the solids isolated by filtration revealed the
existence of marked differences among them. Thus, the
reactions putatively leading to tetraimines 9 and 11 (Chart 2)
afforded amorphous solids that were insoluble in common
organic solvents. On the other hand, macrocycles 8 and 10
RESULTS AND DISCUSSION
The eight macrocycles considered were attainable through [2 +
] cyclocondensations of the semirigid 1,3- and 1,4-phenylene
■
2
B
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Article
Scheme 1. Synthesis of the Bis-imines 6 and 7
lack of sorption capabilities and the low solubility in nonpolar
solvents exhibited by macrocycles 8−11, we focused on the
synthesis, characterization and study of the cyclohexane-
substituted counterparts.
The macrocyclic tetraimines 1 and 12−14 bear 1,1-
3
cyclohexane substituents at the four sp hybridized carbon
atoms (Scheme 2). Single crystals of 1 (monoclinic, C2/c) as
Scheme 2. Synthesis of the Cyclohexane Substituted
Tetraimines
Chart 2
EtOAc solvate, were obtained from a first crop of 15% yield as
14
already reported. Remarkably, after the initial solid was
removed by filtration, the mother liquor was kept at room
temperature for several days affording additional crops of
EtOAc@1 crystals. A total yield of 55% was reached summing
up the crystals grown in four consecutive crystallizations. This
result suggests that, under heterogeneous reaction conditions,
the equilibrium providing the tetraimine is shifted toward the
product formation by precipitation of EtOAc@1 solvate, which
is insoluble in the reaction medium. In general, the reaction
yields for the synthesis of the macrocycles remained low to
moderate in solvents of different polarity. For example, the
yield of 1 isolated as an amorphous solid at room temperature
was 16% in MeCN, 35% in MeCN/TFA(cat.), <5% in
dichloromethane, and 10% in refluxing MeOH. After removal
under a vacuum (4 × 10− mmHg, 12 h), of the EtOAc trapped
in the EtOAc@1 solid, the resulting empty material 1a retained
a porous structure. The latter material had a relatively low
packing index of 54.39% compared to 72.15% calculated for the
parent EtOAc solvate.
2
Following an identical procedure, we were able to obtain
single crystals suitable for X-ray analysis for macrocycle 13 in
25% yield. Unfortunately, the precipitation-driven strategy was
not effective for the isolation in pure and crystalline form of the
macrocycles 12 and 14. The crude reaction precipitates
obtained in the synthesis of the isomeric macrocycles 12 and
14 were amorphous solids isolated in 16 and 21% yields,
respectively. The ESI-MS analysis of the respective solid
materials revealed the presence of the target [2 + 2]
macrocycles (>70%). In both cases, we observed an intense
ion peak at m/z 838.48 that was assigned to the molecular peak
were isolated in 15 and 22% nonoptimized yields, respectively,
as the exclusive components of the precipitate. The H NMR
1
spectra of 8 and 10 showed sharp signals for the imine protons
at 8.69 and 8.75 ppm, respectively. In addition, we observed
intense peaks at m/z 565.23 in the mass spectra of the solids
+
that were assigned to the isomeric molecular ions [M + H] of
8
and 10, respectively. We crystallized macrocycle 10 by slow
evaporation of a chloroform solution, but the resulting cotton-
like crystals were unsuitable for X-ray analysis. Preliminary
sorption experiments performed on macrocycles 8−11 using
nitromethane as guest were unsuccesful. Thus, owing to the
+
[M + H] together with minor but significant ion peaks at
C
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55.5, 971.5, and 1157.7 m/z ratios, that were assigned to the 2
Article
8
solid state, two pendant cyclohexane residues belonging to
adjacent macrocyclic units are located up and down with
respect to the aromatic cavity and block the formation of pore
channels. In short, the key difference of form 1b or 13
compared to form 1a is that the macrocyclic tetraimines instead
of forming centered columnar assemblies, they are placed into
offset columnar arrangements (Figure 2C−D).
The solid materials 1a, 1b, and 13 are sparingly soluble in
CDCl and totally insoluble in polar solvents such as MeOH-d
or DMSO-d . Even achieving solutions of these solids in
concentrations suitable for NMR studies is challenging. To
dissolve crystalline samples of 1a, 1b and 13 in CDCl required
1
+
2, 2 + 3, and 3 + 2 linear oligomers, respectively. The H
NMR spectra of the solids dissolved in CDCl also supported
3
the presence of the macrocyclic component as the major
species. All our attempts to purify the macrocyclic tetraimines
1
2 and 14 by column chromatography or by recrystallization in
20
different solvent mixtures were unsuccessful.
Compounds 1 and 13 are constitutional (structural) isomers
with similar geometric size and shape however their packing in
the solid state is markedly different. Whereas 1 is obtained as an
ethyl acetate solvate EtOAc@1, in identical experimental
conditions 13 precipitated in a denser form that shows
resemblance with 1b (triclinic, P1) the nonporous form of
polymorph 1 (Figure 2).
3
4
6
3
long times and the help of vigorous shaking, high temperature,
and/or sonication. Under these premises, the H NMR spectra
in CDCl solutions of both, 1a and 1b recorded at room
1
3
temperature displayed narrow well-resolved signals that were
completely superimposable. This result indicated that the
dissolution process promoted the conversion of macrocycle 1
into a single conformer or to a mixture of conformers that
interconverted rapidly on the NMR time scale. Given that 1b is
the thermodynamic form of 1, we propose that the energetically
more favorable conformation of 1 in solution must be similar to
the one adopted in form 1b.
To support the hypothesis of the presence of a preferred or
exclusive stereoisomer in solution, we performed the
condensation reaction affording 1 in refluxing MeOH. In this
solvent, the templating effect of the EtOAc disappears, and the
condensation reaction of macrocycle formation is much faster.
After 6 h at reflux, the resulting solid product was collected by
1
13
1
1
filtration and analyzed by NMR ( H and C, H− H COSY,
ROESY, HSQC). The spectroscopic analyses revealed the
presence of two sets of separate proton signals that were not
involved in chemical exchange on the ROESY time scale. We
assigned these two sets of proton signals to two different
macrocyclic conformers of the teraimine, 1 and 1′ produced
under these conditions. By integration of selected signals, we
assigned a ratio of 60/40 of the two conformers. We also
observed additional proton signals in the proton spectrum that
corresponded to minor amounts of open and linear oligomers.
The ESI-HRMS analysis of the mixture of cyclic conformers 1
+ 1′, showed an intense peak at m/z 837.4891 in complete
agreement with the formula C H N that we assigned to [M +
Figure 2. ORTEP representation (50% probability displacement
ellipsoids) of the X-ray crystal structures of (A) 1b, and (B) 13.
Hydrogen atoms are drawn as fixed-size spheres of 0.15 Å radius. (C)
and (D) Side and top views of the spatial arrangement of three
consecutive macrocyclic units in the crystal packing of 1b and 13,
respectively.
60
61
4
+
H] , the molecular ion for the macrocyclic tetraimine 1
(Supporting Information). Taken together, these results
indicated that under the harsh reaction conditions of refluxing
MeOH two diastereomeric conformers were formed and that
they were involved in a slow interconversion process on the
chemical shifts and ROESY time scales. Unfortunately, all our
attempts to isolate the minor stereoisomer 1′, through
Having four aliphatic centers in their structures, macrocycles
and 13 are indeed nonplanar. In principle, they can exist in
1
solution as different conformers. In the solid state, we have
identified so far two forms for 1, namely 1a and the denser and
nonporous counterpart 1b. The macrocycle 1 adopts slightly
different conformations in the solid state of the two forms. The
polymorph 1b is obtained by heating crystals of 1a at around
fractional recrystallization or column chromatography (Al
O ;
3
2
1
4
1
70 °C. Remarkably, in this work we have promoted the same
CHCl ), were unsuccessful and resulted in the isolation of
3
irreversible homotropic transition by just soaking crystals of
EtOAc@1 in MeOH for 48 h at room temperature.
mixtures containing both stereoisomers probably due to partial
interconversion.
In close analogy to 1b, the X-ray structure of 13 (monoclinic,
In order to evaluate the thermodynamic preference of the
P2 /c) revealed a flattened chairlike conformation for the
two conformers, we heated a CDCl solution of the mixture of
1 and 1′ at 45 °C. We used H NMR spectroscopy to monitor
1
3
1
macrocycle governed by aromatic stacking interactions in the
solid. In the crystal lattice, each p-phenylene ring of 13 is
involved simultaneously in two aromatic interactions, one
stacked offset (Rcen = 3.644 Å) and the other perpendicular T-
shaped (Rcen‑H = 2.693 Å). There are also several H(arom.)···
H(alif.) dispersive contacts arising from the cyclohexyl residues
at distances in the range 2.4−3.0 Å, well within the standard
the changes of the mixture with time. We observed a gradual
depletion of the proton NMR signals assigned to the less
abundant conformer 1′ and the concomitant increase of the
proton signals assigned to 1 (Supporting Information). At this
point, owing to the dynamic nature of the imine bonds, we
cannot rule out the possibility of interconversion between 1′
and 1 through a ring-opening-ring-closing reaction mechanism
1
6a
values for attractive dihydrogen contacts for alkanes. In the
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1
Figure 3. (A) Transimination reaction of macrocycle 1 with n-BuNH in CDCl at 25 °C. (B) Representative sections of the H NMR (600 MHz)
2
3
spectra registered at time intervals. The letters indicate NMR assignation. (C) Graphical representation showing the evolution of the imine-exchange
with time.
or by imine metathesis. It is known that imine metathesis is
21
catalyzed by small amounts of primary amines. In fact, the
addition of an excess of n-butylamine to a solution of the
macrocyclic tetraimine 1 in CDCl3 at room temperature
produced the complete transimination of 1 into the bis-imine
1
5 (Figure 3).
In summary, the solid 1a derived from the macrocycle 1 is
the only porous material suitable for sorption experiments.
Among the potential guests for liquid−solid sorption experi-
ments, phthalates are interesting due to environmental and
2
2
health issues. In this work, we used different phthalates to
investigate the geometric boundaries of 1a. The sorption
experiments were carried out by moving several prismatic
crystals of both, the solvate EtOAc@1 or the apohost 1a into a
test vial containing the phthalate under test. The lower density
of the EtOAc@1 crystals (1.089 g/mL) compared to diethyl
phthalate (EtPh) (1.12 mg/L), allowed us to visually monitor
the progress of the guest exchange (Figure 4A). Soon after
being in contact with EtPh the crystals of EtOAc@11 started to
sink into the EtPh liquid.
The solid-state structure of EtPh@1 was solved by single-
crystal X-ray diffraction (Supporting Information). The analysis
of the X-ray data showed that the EtPh molecules are in
disordered positions within the channels of 1, thus indicating
the weak interaction existing between the walls of the porous
material and the included guest. In fact, the uptake of the guest
molecule could be reversed by just moving the EtPh@1 or the
EtOAc@1 crystals into a vial containing fresh ethyl acetate or
diethyl phthalate, respectively. After several EtOAc-EtPh
exchanging cycles, we did not observe any morphological
Figure 4. (A) Sequential images showing the progress of the diethyl
phthalate uptake by EtOAc@1 crystals. The images were taken every 5
min (ttot = 50 min). (B) ORTEP representation (50% probability
displacement ellipsoids) of the X-ray crystal structures of EtPh@1
crystals. The disorder affecting the EtPh molecule was removed for
clarity. The inset shows the relative orientation of two molecules of
EtPh inside the channel.
E
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alteration of the crystal structure of EtOAc@1. However, if the
crystals EtPh@1 were immersed in MeOH instead of EtOAc,
the exchange process became irreversible due to the irreversible
transformation of 1a into the nonporous polymorph 1b. The
irreversible release of EtPh by MeOH was monitored by H
NMR spectroscopy showing that desorption was complete after
issue is that only one member of this series of isomeric
macrocycles showed porosity.
In this article, the synthesis of the porous macrocycle 1 has
been modified to shorten the precipitation of the key EtOAc
solvate EtOAc@1. Furthermore, we demonstrated for the first
time the use of 1 both, as the EtOAc solvate or the apohost 1a,
for the preferential liquid−solid adsorption of diethyl phthalate
over other commercial phthalates. Thus, expanding the use of a
POM material based on the macrocycle 1 toward the reversible
adsorption of sizable molecules in the liquid state at room
temperature.
1
12 h. Similar results were obtained using the apohost 1a instead
of the solvate EtOAc@1. In this case, the adsorption process of
EtPh on 1a was slow, and a steady rise of the amount of
included EtPh guest on 1a was observed until saturation took
place after 48 h. It has to be noted that the adsorption rate on
1
a is much faster with other small molecules. For instance,
3
adsorption of nitromethane (55.3 Å ) on 1a was complete in 5
min. In this case, the adsorption of nitromethane was evidenced
by the massive air bubbles displacement from the solid 1a
EXPERIMENTAL SECTION
■
All reagents were reagent grade and were used as purchased. H, 13C
1
13
and 2D NMR spectra (at 300 and 600 MHz) and C (at 75 and 150
(
1
Supporting Information). The crystallographic stoichiometry
:2 for EtPh@1 was also confirmed by a weight loss of 12,9%
MHz) spectra were recorded on 300 and 600 MHz spectrometers in
CDCl solutions at room temperature. The residual proton signal was
3
in the thermogravimetric analysis of EtPh@1 and by
integration of the proton spectrum registered on a dissolved
sample of EtPh@1 (Supporting Information). The maximum
available void volume per macrocycle is 274 Å and the
molecular volume calculated for EtPh is 232 Å thus, taking
used as reference. Chemical shifts (δ) are given in ppm and coupling
1
1
constants (J) in Hz. Peaks assignments were aided by H− H COSY,
HMQC and HMBC experiments. Mass spectra were registered on
Orbitrap mass spectrometer equipped with an electrospray module.
General Procedure for the Synthesis of the Bis-imines. The
bis-propargyl diamine (0.21 g, 0.65 mmol) was dissolved in MeOH
(20 mL) together with benzaldehyde (139 μL, 1.36 mmol). The
resulting solution was refluxed for 8 h. The precipitation of a solid
occurred after cooling to room temperature. The product was filtered,
washed with MeOH and dried under a vacuum.
3
3
3
into account the 1,2 stoichiometry of EtPh@1, (232 Å /2 ×
3
2
74 Å ) gives a packing coefficient close to 0.42. This value is
smaller than the 55% rule of Mecozzi and Rebek for the
23
optimal filling of capsules. The molecular volumes of other
common phthalates, namely dibutyl phthalate (BuPh, 305 Å ),
butyl benzyl phthalate (BnPh, 363 Å ), and 2-diethylhexyl
phthalate (OcPh, 451 Å ) are higher than that of EtPh, and
their packing coefficients are 0.55, 0.66, and 0.82, respectively.
Hence, a preferential adsorption of EtPh over the other bulkier
phthalates is expected. Pair-wise competitive sorption experi-
ments were performed with crystals of EtOAc@1 and 1:1
molar ratio liquid mixtures of pairs of phthalates. After 48 h of
3
1
,3-Dialkynylbenzene bis-imine 6. White solid, 0.2 g, 61% yield.
3
1
mp = 121−124 °C. H NMR (300 MHz, CDCl , ppm) δ 8.84 (s, 2H),
3
3
7.82 (m, 4H), 7.64 (s, 1H), 7.47 (d, J = 7.2 Hz, 2H), 7.42 (m, 6H),
7.33 (t, J = 7.95 Hz, 1H), 1.87 (m, 20H); 13C NMR (75 MHz, CDCl3,
ppm) δ 158.2, 136.7, 134.8, 131.5, 130.6, 128.6, 128.5, 123.7, 92.0,
8
4
2
8.7, 63.6, 39.9, 25.5, 23.2; ESI-HRMS(+) m/z (%): calc. C H N
36 37 2
+
97.2957; exp. 497.2949 [M + H] . Anal. Calcd for C H N ·1/
36 36
2
H O: C, 85.5; H, 7.38; N, 5.54. Found: C, 85.16; H, 7.34; N, 5.55.
2
1
1,4-Dialkynylbenzene bis-imine 7. Yellow solid, 0.25 g, 72%
evolution at room temperature, the H NMR analysis recorded
1
yield. mp = 110−112 °C; H NMR (300 MHz, CDCl , ppm) δ 8.86
3
on the dissolved samples showed the selective adsorption of
EtPh over BuPh and BnPh in a 3:1 and 5:1 ratio, respectively.
On the other hand, the absorption of OcPh was never detected.
The size and volume of OcPh are larger than the geometrical
limits imposed by the porous EtOAc@1 material. All together,
the sorption experiments serve to highlight the existence of a
direct relationship between the volumes of the included guests
and the sorption capabilities of the porous solids EtOAc@1
and 1a.
(s, 2H), 7.84 (m, 4H), 7.50 (s, 4H), 7.45 (t, J = 3 Hz, 6H), 1.87 (m,
13
2
0H); C NMR (75 MHz, CDCl , ppm) δ 158.2, 136.7, 131.7, 130.7,
3
128.7, 128.5, 123.1, 93.1, 89.2, 63.7, 39.9, 25.6, 23.3; ESI-HRMS(+)
+
m/z (%): calc. C H NaN 519.2776; exp. 519.2770 [M + Na] . Anal.
36
36
2
Calcd for C36
.30; N, 5.65.
Improved Synthesis of the Macrocyclic Tetraimine 1
EtOAc@1). Terephthalaldehyde, (0.15 g, 0.468 mmol) and 1,1′-
1,3-phenylenebis(ethyne-2,1-diyl))bis(cyclohexan-1-amine) (0.063 g,
.468 mmol), were dissolved in MeOH (55 mL). The resulting
H N : C, 87.05; H, 7.31; N, 5.64. Found: C, 86.74; H,
36 2
7
(
(
0
solution was refluxed for 5 h. After this period, the crude was
evaporated under reduced pressure. The isolated solid was then
suspended in EtOAc, and filtered. The solution was covered with
parafilm and, after 5 days, 38 mg of the crystalline porous material was
isolated (yield 10%). The remaining solution was covered again
obtaining additional crops of the crystalline product as the EtOAc
solvate (final practical yield ∼40−50%). This procedure is more
CONCLUSIONS
■
The condensation of 1,3- and 1,4-phenylene bis-propargylic
diamines with terephthalaldehyde or isophthalaldehyde resulted
in the formation of tetraimine macrocycles. The condensations
were reversible but in all cases the products arising from a [2 +
2
] cyclocondensation were predominant. In EtOAc as the
14
convenient than the original one as it reduces to a half the time spent
solvent, the yields were low to moderate, but they provided the
macrocycles as solid products readily isolable by filtration or
decantation. However, several issues emerged. First, the
unsubstituted macrocycles were very insoluble in all common
organic solvents precluding any further study on them. This
issue was solved synthesizing their cyclohexane-substituted
equivalents. These macrocycles, featuring four 1,1-cyclohexane
residues, were slightly soluble in chloroform, but they proved
insoluble in EtOAc, MeOH, MeCN and DMSO. The lack of
solubility cannot be considered disadvantageous since the
macrocycles are intended for constructing porous organic
molecular solids (POMs). The second, and more important
on crystallization.
General Procedure for the Synthesis of the Isomeric
Macrocyclic Tetraimines. A typical procedure was as follows: a
solution of the propargyl diamine (400 mg, 1.248 mmol) and the
dialdehyde (169 mg, 1.248 mmol) in EtOAc (120 mL) was placed in a
2
50 mL Erlenmeyer flask. The flask was covered with parafilm and let
aside at room temperature for evolution. After a variable period
ranging from several days to 8 weeks, the precipitated products were
isolated by simple decantation of the solution. The solid whether
amorphous or crystalline was washed with fresh EtOAc and dried.
Macrocyclic Tetraimine 8. White amorphous solid, (0.18g, 15%).
mp >250 °C (dec.). H NMR (600 MHz, CDCl , ppm), δ: 8.69 (s,
4H), 7.88 (s, 8H), 7.71 (s, 2H), 7.40 (t, J = 6.9 Hz, 6H), 4.77 (s, 8H);
1
3
F
DOI: 10.1021/acs.joc.6b00768
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
ESI-HRMS(+) m/z (%): calc. C H N 565.2392; exp. 565.2379 [M
3982 reflections measured, 3982 independent reflections (Rint =
40
29
4
+
13
+
H] . The C NMR spectrum could not be registered due to the low
0.0000). The final R values were 0.0674 (I > 2σ(I)). The goodness of
1
2
solubility of this compound.
fit on F was 1.052.
Macrocyclic Tetraimine 10. White amorphous solid (0.28 g,
1
2
(
2
2%). mp >250 °C (dec.). H NMR (600 MHz, CDCl , ppm), δ: 8.75
3
ASSOCIATED CONTENT
■
s, 4H), 8.01 (d, J = 7.8 Hz, 4H), 7.97 (s, 2H), 7.51 (t, J = 7.2 Hz,
H), 7.47 (s, 8 H), 4.81 (s, 8H); 13C NMR (150.9 MHz, CDCl , ppm)
*
S
Supporting Information
3
δ 161.3, 136.6, 132.0, 131.3, 129.3, 129.2, 123.1, 87.9, 86.0, 47.7; ESI-
HRMS(+) m/z (%): calc. C H N 565.2392; exp. 565.2373 [M +
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b00768.
1H, 13C NMR and 2D spectra of the new compounds,
40
29
4
+
H] ; Anal. Calcd for C H N : C, 85.08; H, 5.00; N, 9.92. Found: C,
40
28
4
8
4.80; H, 4.99; N, 9.95.
Macrocyclic Tetraimine 12. White amorphous solid, (0.16g,
6%). mp >250 °C (dec.). H NMR (600 MHz, CDCl , ppm), δ
and additional experimental details. (PDF)
Crystal structure for 7, 13 and EtPh@1. (ZIP)
1
1
3
(
ppm): 8.87 (s, 4H), 8.19 (s, 2H), 7.86 (s, J = 7.8 Hz, 4H), 7.63 (s,
2
H), 7.45 (d, J = 7.5 Hz, 4H), 7.32 (t, J = 4.8 Hz, 4H), 1.80 (m, 40H);
AUTHOR INFORMATION
ESI-HRMS(+) m/z (%): calc. C H N 837.4891; exp. 837.4891 [M
+
solubility of this compound.
■
6
0
61
4
+
13
H] . The C NMR spectrum could not be registered due to the low
Corresponding Author
E-mail: antoni.costa@uib.es. Tel.: +34 971 173266. Fax: +34
71 173426.
*
Macrocyclic Tetraimine 13. Yellow crystals, (0.25g, 25%). mp
9
1
>
250 °C (dec.). H NMR (600 MHz, CDCl , ppm), δ: 8.85 (s, 4H),
3
Notes
8
.19 (d, J = 7.2 Hz, 4H), 7.62 (s, 2H), 7.48 (s, 10H), 1.81 (m, 40H);
1
3
C NMR (75 MHz, CDCl , ppm) δ 157.3, 136.9, 133.1, 131.8, 129.3,
The authors declare no competing financial interest.
3
1
28.2, 123.1, 92.53, 89.5, 63.9, 39.9, 29.8, 25.5, 23.2; ESI-HRMS(+)
+
m/z (%): calc. C H N 837.4896; exp. 837.4905 [M + H] . Anal.
60
60
4
ACKNOWLEDGMENTS
■
Calcd for C H N ·H O: C, 84.27; H, 7.31; N, 6.55. Found: C,
6
0
60
4
2
Financial support from the Spanish Ministry of Economy and
Competitiveness (CTQ2014-57393-C2-1-P and CONSOL-
IDER-INGENIO 2010 CSD2010-00065, FEDER funds) are
gratefully acknowledged. C. L. thanks CAIB and FSE for a
predoctoral fellowship.
8
4.32; H, 7.29; N, 6.56.
Macrocyclic Tetraimine 14. White amorphous solid, (0.22 g,
1
2
(
1%). mp >250 °C (dec.). H NMR (600 MHz, CDCl , ppm), δ: 8.84
3
s, 4H), 7.85 (s, 8H), 7.47 (s, 8H), 1.83 (m, 40H); ESI-HRMS(+) m/
+
13
z (%): calc. C H N 837.4896; exp. 837.4885 [M + H] . The
C
60
61
4
NMR could not be registered due to the low solubility of this
compound.
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2
4
■
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3
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1
5
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469775): C H N , M = 496.67, monoclinic, a = 9.710(10) Å, b =
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66
67
4
2
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9
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469781): C H N , M = 837.12, monoclinic, a = 10.9226(8) Å, b =
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DOI: 10.1021/acs.joc.6b00768
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
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DOI: 10.1021/acs.joc.6b00768
J. Org. Chem. XXXX, XXX, XXX−XXX