Scalable preparation and property investigation of a cis-cyclobutane-1,2-dicarboxylic acid from β-trans-cinnamic acid

Article abstract of DOI:10.1039/c8cc08017h

Scalable synthesis of β-truxinic acid (CBDA-4) was accomplished by capturing and photodimerizing a metastable crystalline solid of trans-cinnamic acid. This synthetic approach builds a foundation for investigating the properties and applications of the us

Full text of DOI:10.1039/c8cc08017h

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Scalable preparation and property investigation
of a cis-cyclobutane-1,2-dicarboxylic acid from
b-trans-cinnamic acid†
Cite this: Chem. Commun., 2019,
55, 214
Received 8th October 2018,
Accepted 22nd November 2018
Houssein Amjaour,‡ Zhihan Wang,‡ Micah Mabin, Jenna Puttkammer,
Sullivan Busch and Qianli R. Chu
*
DOI: 10.1039/c8cc08017h
rsc.li/chemcomm
Scalable synthesis of b-truxinic acid (CBDA-4) was accomplished by 1,3-trimethylene diester for photodimerization, and then hydrolyzing
capturing and photodimerizing a metastable crystalline solid of the ester dimer back to CBDA-4.5–7 Even in a recent development
trans-cinnamic acid. This synthetic approach builds a foundation using transition metal-catalyzed enantioselective synthesis of
for investigating the properties and applications of the useful cyclobutane derivatives, CBDA-4 was only a minor product.8
diacid. The X-ray crystal structure of CBDA-4 was determined Thus, a simple, reliable, and scalable preparation method for
for the first time. The cyclobutane ring in CBDA-4 was cleaved CBDA-4 is highly desirable.
upon heating, making it a promising building block for thermally
recyclable/degradable materials.
It has been known for about a century that both CBDA-1
(also known as a-truxillic acid) and CBDA-4 (also known as
b-truxinic acid) can be synthesized from two polymorphs: a- and
Dicarboxylic acids have extensive applications in many different fields b-trans-cinnamic acid, respectively, in the solid state. However, it
such as polymers, metal–organic materials, and medicines.1 Com- has also been documented that the metastable crystalline b-form
pared to the widely-used diacids (e.g., phthalic acid, succinic acid, and (head-to-head packing) of trans-cinnamic acid readily transforms
adipic acid), cyclobutanedicarboxylic acids (CBDAs) are unfamiliar to to the stable a-form (head-to-tail packing).7b,9 The low energy
many researchers, especially those working in materials science.2 barrier from the b-form to the a-form renders reliable synthesis
CBDAs and their derivatives represent promising building blocks in of CBDA-4 challenging, because only the b-form gives CBDA-4
materials mainly because they can be readily produced from commer- after photodimerization while the a-form leads to CBDA-1, which
cially available starting materials, including many biobased chemicals, also explains the conflicting experimental results about CBDA-4
and have desired properties (e.g. cleavability). Recent studies have synthesis in the literature.9d,10
demonstrated that CBDAs can be used in producing both thermo-
Herein, we report a simple, dependable, and scalable pre-
plastics and thermosets with excellent properties.3 In these polymers, paration method for CBDA-4 (Scheme 1). Commercially available
CBDA served as either a diacid monomer or cross-linker. Fig. 1 shows trans-cinnamic acid (m.p.: 133 1C) was first melted and heated in an
two examples of CBDAs that have been used in polymer synthesis oven at 180 1C for 30 minutes. It was then dissolved in a small
together with CBDA-4, (1R,2S,3R,4S)-rel-3,4-diphenyl-cyclobutane-1,2- amount of DMF and added into ice water with stirring. Blacklight
dicarboxylic acid, which is the focus of this work. Just like CBDA-2, irradiation of the slurry mixture, which contained the metastable
with its structural similarity to o-phthalic acid,4 CBDA-4 can be a crystalline b-form of trans-cinnamic acid, led to the formation of
useful building block with many applications in materials. Recently, CBDA-4. This procedure was repeated dozens of times at a 5 g scale
studies have also shown that CBDA-4 and its derivatives have and has been successfully extended to 1 g and 50 g scales. While
antinociceptive activities,5 and can be used as phthalate-free internal the detailed procedure is included in the ESI,† it is worthwhile
donors in Ziegler–Natta catalysts for propylene polymerization.6
However, researchers have had to take a detour to make CBDA-4
by first converting trans-cinnamic acid to its p-nitrophenyl ester or
Department of Chemistry, University of North Dakota, Grand Forks, ND 58202,
USA. E-mail: chu@chem.und.edu
† Electronic supplementary information (ESI) available: Experimental details,
characterization and properties of b-trans-CA and CBDA-4. CCDC 1857653. For
ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
Fig. 1 Examples of CBDAs: trans-1,3-CBDA and cis-1,2-CBDA. The box
c8cc08017h
highlights the focus of this work.
‡ These authors contributed equally to this work.
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Scheme 1 The facile and scalable preparation of CBDA-4.
to mention here that skipping the step of melting and heating
trans-cinnamic acid could lead to the formation of CBDA-1. It is
also important to add the cinnamic acid/DMF solution directly
into the ice-water solution, rather than on the top of the ice
floating on the water, to avoid formation of any seeds of the
stable a-trans-cinnamic acid. Otherwise, this could also lead to
the formation of CBDA-1 after photoreaction.3b
Fig. 2 The phase transformation of b- to a-trans-cinnamic acid at 50 1C.
The b-form was prepared by precipitating a 5 mL DMF solution of 5 g
of trans-cinnamic acid in 240 mL of ice water.
Powder X-ray diffraction (PXRD) analysis confirmed the
‘‘head-to-head’’ b-form of trans-cinnamic acid precipitated
from the ice-water solution, since its powder pattern was nearly
identical to the simulated pattern generated from the single-
crystal diffraction data (ESI,† Fig. S8).9b Grinding should be
avoided when preparing the sample for PXRD because it can
easily turn the metastable b-trans-cinnamic acid into the stable
a form. A knife can be used to gently cut the precipitate into
smaller particles for PXRD experimentation if necessary.
The phase transformation from b- to a-trans-cinnamic acid was
studied by PXRD and DSC. b-Form powder was heated to 50 1C and
scanned after different time periods. The results illustrated that the
b-form steadily converts to the a-form in 2.5 h. The characteristic
peaks of b-trans-cinnamic acid at 5.61, 15.61, 16.91, 23.61, 26.61, and
27.01 faded gradually upon heating, while new peaks appeared
at 9.81, 15.11, 18.51, 21.81, 25.41, and 29.51, which were attributed
to a-trans-cinnamic acid (Fig. 2). It is important to point out that
the transformation rate depends on the size of the crystals, with
smaller crystals having a faster rate.9c The easy transformation from
b- to a-form might explain why the two polymorphs had almost
the same melting ranges (133.5–134.4 1C for the a-form and
133.2–134.0 1C for the b-form) and DSC curves (ESI,† Fig. S9),
because part of the metastable b-trans-cinnamic acid was converted
to the stable a-form during the heating process while the melting
point or DSC curve was being measured.9a
of CBDA-4, two new doublets (d: 4.22 and 3.82 ppm) appeared
compared with the spectrum of cinnamic acid, which corresponded
to the cyclobutane ring in CBDA-4 with mirror symmetry (Fig. 3). The
1H NMR of CBDA-1 is also included in Fig. 3 for comparison. The
two doublet-of-doublets peaks around 4.30 and 3.83 ppm are
consistent with the center symmetry of CBDA-1.12,13b,c
Plate-shaped single crystals of CBDA-4 were obtained in aceto-
nitrile solution containing a tiny amount of acetic acid at room
temperature. The X-ray single crystal structure of CBDA-4 was
reported for the first time (Fig. 4). The crystal structure revealed
the orientation of the adjacent 1,2-dicarboxylic groups on the
cyclobutane ring, showing its structural similarity to o-phthalic acid
and its potential to serve as a diacid building block in materials.3a,4b
The cyclobutane ring in CBDA-4 adopts a 201 puckered conforma-
tion in the solid state, which is different from the planar cyclobutane
ring of CBDA-1 in its crystal.3b,12,13c The angles in the cyclobutane
ring are 87.82(9), 88.21(9), 87.68(9), and 88.80(9)1, which indicate
the ring strain in the structure. In addition, it was shown that
a supramolecular helix self-assembles along the b axis via
The photoreaction was started at 0 1C when the b-trans-
cinnamic acid precipitated from the ice-water solution. It was fine to
allow the reaction mixture to warm up to room temperature
gradually once the ice in the mixture had melted. Irradiating with
blacklight was continued until the dimerization had completed. The
photodimerization was performed using residential blacklights,
which represent an ECO-UV irradiation source.11 Regular lab glass-
ware (e.g., round-bottom flask, beaker, and Erlenmeyer flask) were
used for the photoreaction because about 90% of the blacklight is
transmitted through the glass.12 The completion of dimerization
was indicated in FT-IR spectra by the disappearance of the bands at
1627 cmÀ1 (CQC, stretching) and 976 cmÀ1 (CQC–H, out of plane
bending), and shifting of the band at 1671 cmÀ1 (CQO, stretching)
to 1697 cmÀ1 12,13
washed with a small amount of ethanol to give a white powder,
.
Subsequently, the mixture was filtered and
Fig. 3 Comparison of the 1H NMR spectra of CBDA-4 (top) and CBDA-1
which was confirmed as CBDA-4 by NMR. In the 1H NMR spectrum (bottom) collected in DMSO-d6. Insets are magnified range from 3.6 to 4.5 ppm.
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Fig. 5 DSC curve recorded with a heating rate of 20 1C minÀ1 under N2
atmosphere.
Fig. 4 X-ray structure of CBDA-4: (a) X-ray single crystal structure in Oak
Ridge Thermal Ellipsoid Plot (ORTEP) representing at 50% electron density.
(b) Cyclobutane-1,2-diacid moiety in CBDA-4 with inner angle 87–881.
The cyclobutane ring is highlighted in blue for clarity. (c) Cyclobutane
moiety adopted 201 puckered conformation. (d) Front view and side view
of supramolecular helix via hydrogen bonds. Hydrogens are omitted in all
three images. The phenyl group and half of the cyclobutane ring are
omitted in the last two images for clarity.
During the subsequent 2nd and 3rd heating–cooling cycles, the
sample was heated and cooled again under the same condi-
tions from 30 1C to 170 1C. A new endothermic peak appeared
repeatedly around the melting point of trans-cinnamic acid in
the 2nd and 3rd heating–cooling cycles, showing the possibility
of thermal cleavage of the CBDA-4 at high temperature. To
figure out what exactly happened to CBDA-4 around 280 1C, a
the intermolecular hydrogen bonding between carboxylic acid sample of CBDA-4 was added to a test tube and heated to 300 1C
groups (OCQOÁ Á ÁOOH = 2.680(2)–2.694(2) Å, Fig. 4d), showing the under argon protection in a sand bath for 15 min. During this
potential of CBDA-4 in preparing supramolecular materials such process, colourless crystals were formed on the test tube walls
as hydrogen-bonded organic frameworks (HOFs)14 and metal– which were analyzed by NMR. In the 1H NMR spectrum, it was
organic materials (MOMs).15
found that the peaks around 4.22 and 3.82 ppm disappeared
The preparative method used readily provided us with pure and two new doublet peaks showed up at 7.58 and 6.52 ppm,
CBDA-4 to study its properties. The CBDA-4 samples were which indicated double bond formation. The 1H NMR spec-
treated with either 6 M NaOH or 6 M HCl aqueous solution trum was identical to that of trans-cinnamic acid (Fig. 6). Based
at 100 1C for 12 h. After workup, 1H and 13C NMR spectra of the on this observation, it was confirmed that the photocycloaddi-
recovered samples showed no change compared to the original tion of trans-cinnamic acid to form CBDA-4 can be reversed by
spectra of CBDA-4, which suggested the cyclobutane ring thermocleavage (Scheme 2). Although it is known that cyclobu-
is stable under base or acid conditions. Thermogravimetric tane rings can be cleaved by using deep UV,17 there have been
analysis (TGA) showed no obvious weight loss below 200 1C and only a few reports on cleavage of the four-membered ring with
5% weight loss around 250 1C (Fig. S11, ESI†). The derivation heat,18 and the potential application of the thermocleavage in
exhibited the temperature of maximum weight loss for CBDA-4 recyclable or degradable materials has not been realized.
as 319 1C. In differential scanning calorimetry (DSC) analysis, This discovery reveals a facile and scalable way to degrade the
no change was observed below the melting point of CBDA-4 diacid CBDA-4 thermally at the end of its life as a polymer
around 208 1C (Fig. 5). Both TGA and DSC suggested that building block.
CBDA-4 is stable at temperature of at least 200 1C, which
In summary, a simple, reliable, and scalable preparation
indicates that its thermostability is suitable for many potential approach for CBDA-4 has been developed, which offers a direct
applications. Despite the ring strain of the cyclobutane, CBDA-4 and facile way to access this versatile diacid building block from a
is reasonably stable, presumably due to the fact that the [2+2] commercially-available starting material. Synthesis of different
photocyclization and corresponding reverse reaction are generally useful targets (e.g., CBDA-1 and CBDA-4) from the same starting
thermally forbidden,16 which means a high thermal energy barrier materials just by changing the crystallization/precipitation condi-
has to be overcome to break the four-membered ring once it is tions is challenging, but appealing due to its potential ability to be
formed by photoreaction.
highly useful, environmentally efficient and economically plausi-
It was exciting to see a 2nd endothermic peak appear around ble. The synthetic strategy and tricks that are employed in
280 1C in the DSC curve of CBDA-4 shown in Fig. 5. The sample capturing and photodimerizing a metastable crystalline solid of
was cooled down to 30 1C after heating it at 300 1C for 5 min. trans-cinnamic acid at low temperature might be utilized for
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morphs. The single crystal structure of CBDA-4 was reported for
the first time, confirming the orientation of the two carboxylic
acid groups, and the stability tests showed its potential as a diacid
building block with a variety of applications. The thermal cleavage
of CBDA-4 discovered in this study might open a new gate for
making thermally recyclable and/or degradable materials, such
as sustainable polymers, as plastic wastes are causing severe
environmental tribulations both on land and in the ocean.19
We are grateful for the financial support of this work by the
National Science Foundation Grant (NSF EPSCoR Award IIA-1355466).
Conflicts of interest
There are no conflicts to declare.
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