2u202f+u202f2 Dimerization of cinnamylidene malonic acid: A structural and kinetic study

Article abstract of DOI:10.1016/j.tetlet.2018.07.038

Cinnamylidene malonic acid was synthesized and its crystal structure obtained. The dicarboxylic acid hydrogen-bonding motif of this structure consists of catemer chains that lie along the c- glide plane. A photo induced 2 + 2 cycloaddition occurred upon exposure of the crystals to UV light which resulted in the destruction of the crystal. The structure of the photo products were determined by IR and NMR analysis. The regio- and stereo-chemistry of the photoproduct can be rationalized by examining the relative orientation and symmetry relating reacting molecules within the crystal structure. A kinetic study demonstrated first order reaction kinetics which is consistent with a reaction occurring under topochemical control.

Full text of DOI:10.1016/j.tetlet.2018.07.038

Accepted Manuscript
2+2 dimerization of cinnamylidene malonic acid: A structural and kinetic study
Shana Weathersby, Brian Dinkelmeyer, Robert Pike, Scott Huffman
PII:
S0040-4039(18)30912-2
https://doi.org/10.1016/j.tetlet.2018.07.038
TETL 50147
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Accepted Date:
24 May 2018
13 July 2018
Please cite this article as: Weathersby, S., Dinkelmeyer, B., Pike, R., Huffman, S., 2+2 dimerization of
cinnamylidene malonic acid: A structural and kinetic study, Tetrahedron Letters (2018), doi: https://doi.org/
10.1016/j.tetlet.2018.07.038
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
2+2 dimerization of cinnamylidene malonic acid: A strucLtuearavel athnids akrienaetbilcasntkufdoyr.abstract info.
Shana Weathersby, Brian Dinkelmeyer, Robert Pike, Scott Huffman

1
Tetrahedron Letters
2+2 dimerization of cinnamylidene malonic acid: A structural and kinetic study.
Shana Weathersby,a Brian Dinkelmeyer,a  Robert Pike,b Scott Huffmana
aWestern Carolina University, Dept. of Chemistry and Physics, Cullowhee, NC 287723.
bCollege of William and Mary, Dept. of Chemistry, Williamsburg, VA 23187-8795.
ARTICLE INFO
ABSTRACT
Cinnamylidene malonic acid was synthesized and its crystal structure obtained. The
dicarboxylic acid hydrogen-bonding motif of this structure consists of catemer chains that lie
along the c- glide plane. A photo induced 2+2 cycloaddition occurred upon exposure of the
crystals to UV light which resulted in the destruction of the crystal. The structure of the photo
products were determined by IR and NMR analysis. The regio- and stereo-chemistry of the
photoproduct can be rationalized by examining the relative orientation and symmetry relating
reacting molecules within the crystal structure. A kinetic study demonstrated first order reaction
kinetics which is consistent with a reaction occurring under topochemical control.
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
topochemical
photochemistry
2+2 dimerization
2009 Elsevier Ltd. All rights reserved.
———
 Corresponding author. Tel.: +0-000-000-0000; fax: +0-000-000-0000; e-mail: author@university.edu

2
Tetrahedron
Introduction
kinetic study strongly suggest that the reaction is under lattice
control.
It was discovered in our lab that crystals of cinnamylidene
malonic acid undergo a 2+2 topochemical cycloaddition reaction
upon exposure to uV light. Similar reactivity was previously
reported for cinnamylidene cyanoacetate crystals.1 Topochemical
reactions are solid state reactions whose outcome are under
lattice control. In these reactions, the nature of the molecular
packing within the crystal determines the reactivity and the
structure of the products formed. The constraining environment
of the crystal lattice necessitates that reactions occur between
nearest neighbors and with minimal atomic and molecular
movement.2 The relative orientation of reacting molecules is
retained in the products. A hallmark of single-crystal to single-
crystal topochemical reactions is the incorporation and retention
of crystallographic symmetry in the product formed.
Results and Discussion
Cinnamylidene malonic acid was synthesized in 58% yield by
condensing cinnamaldehyde with malonic acid in pyridine.9
Crystals were grown by slow evaporation from ethanol and
produced long yellow needles. The X-ray crystal structure of the
cinnamylidine malonic acid was determined and the details of the
data collection and refinement are summarized in Table 1. The
compound crystallized in the monoclinic space group P21/c with
four molecules in the unit cell.10
Interestingly, the dicarboxylic acids do not form the typical
hydrogen bonded dimers related by inversion centers. The
dicarboxylic acid moieties form an infinite catameric hydrogen
bonded tape with adjacent molecules lying on opposite sides of
the c-glide symmetry operator. One hydrogen bond donors is
engaged in an intramolecular bond between the carboxylic acid
moieties. The remaining H-bond donor engages in a syn-syn anti
intermolecular hydrogen bond(Fig. 2).11
The geometric criteria for topochemical cycloadditions of
alkenes have been well established.3 Reaction occurs between
nearest neighbors in a stack and occurs with minimal atomic and
molecular movement. For 2+2 cycloadditions, the reacting π-
bonds must be parallel and within 4.2Å for reaction to take place.
Ideally, the planes containing reacting π bonds should be aligned
so that π overlap is maximized. This occurs when the planes of
the π-bonds are parallel and reacting carbons are directly over
Neighboring catameric hydrogen-bonded tapes stack via Van
Der Waal forces along the a-axis and are related by inversion
centers. These stacked tapes are related by a 2-fold screw axis
that runs parallel to the b-axis. This results in parallel C=C
moieties which are organized in a head-to-tail arrangement along
the a-axis. The head-to-tail orientation of molecules along the a-
axis in neighboring H-bonded networks play a critical role in
determining the stereo- and regiochemical outcome of the solid
state photoproducts formed upon irradiating the crystals. Figure
3 shows the stacking and orientation of three neighboring
catameric H-bonded networks.
Figure 1. Geometric parameters for 2+2otopochemical dimerization.
Optimal values for reactivity are θ2 = 90 , θ3 = 90o, d = 3.5-4.2 Å
one another (Fig 1). Maximal π overlap is achieved when the
offset angles relating alkene planes are 90o . These angles are
defined as follows: θ2 is the angle formed between reacting
carbons and the axis of the double bond; θ3 is the angle between
an alkene substituent and the newly forming bond (Fig. 1).4
Deviations from these geometric criteria results in diminished
reactivity.
Further refinement of these principles include consideration of
the reaction cavity which consists of the molecules immediately
surrounding the species undergoing reaction.5 Reactions
requiring large amplitude molecular movements would
experience substantial steric interaction with molecules in the
surrounding lattice and would require significant lattice
reorganization to proceed. The steric and lattice reorganization
can be energetically prohibitive and can prevent reaction even if
all of the geometric criteria for topochemical reactivity are met.6
This is why topochemical reactions are not common place.
Figure 2. a) Illustration of a syn-syn-anti intermolecular hydrogen
bond. b) Catameric H-bonded tape with alternating units related
across a glide plane. c) Ortep representation of the catameric syn-
syn-anti hydrogen bonded network along the c-glide.
The kinetics of the lattice controlled reactions differ from
typical solution phase reactions and share similarities with solid-
solid phase transitions which exhibit cooperative effects. The
reaction can be envisioned as a phase transformation between
reactant and product crystalline phases.7 Lattice reorganization
to accommodate the growing product phase acts as the rate
limiting process. The kinetics are influenced more by the
presence of lattice defects which serve as sites for lattice
reorganization than by the inherent reactivity of the functional
groups undergoing reaction. The kinetics often appear pseudo
first order with respect to defect and nucleation sites and often
exhibit cooperative effects.8
Figure 3. Packing diagram of cinnamylidene malonic acid showing
the head-to-tail relationship of neighboring molecules and the
packing of catameric hydrogen bonded networks.
The current work demonstrates another example of a 2+2
topochemical cyclization on a conjugated system. The
stereochemical outcome of the single photoproduct and the
Exposure of the crystals to uV or sun light resulted in
considerable cracking and ultimately caused the crystal to
fragment into a crystalline powder which is not uncommon for
topochemical photoreaction reactions.11 The destruction of the

3
crystals precluded single crystal analysis of the photoproducts.
1H NMR of the crystalline powder indicated that a 2+2
cycloaddition had occurred between C5=C6 units of neighboring
cinnamylidene molecules. The head-to-tail orientation and
inversion center relating monomers in the crystal structure are
maintained in the cyclic dimer (Fig. 4). Further evidence of the
cycloaddition can be seen in the 13C NMR where the C5=C6 peaks
at 123.4 and 143.8ppm do not appear in the spectrum of the
photoproduct and are replaced by peaks at 40.8 and 45.9ppm
which correspond to the C5-C6 carbons of the cyclobutane ring
(supplemental information).
modes of reaction deviate from having ideal angle offset values
for maximal π orbital overlap (θ2 & θ3 ≠ 90o).
Further evidence of a lattice controlled reaction mechanism
comes from kinetic studies of the photochemical reaction.
Infrared spectra were measured on crystalline samples that were
ground into a powder and pressed into windows using BaF2 as a
matrix. BaF2 was selected dueto its non-hygroscopic nature.
The samples were irradiated in a Rayonet Photochemical Reactor
at a wavelength of 250nm. The interior temperature of the
reactor was allowed to equilibrate before introduction of the
sample. Sample temperature was maintained at a fairly constant
24oC ±1 oC. Infrared spectra were collected at regular time
intervals. Each spectra was baseline corrected and normalized on
the carbonyl bands spanning 1725-1680 cm-1.
1
The Figure 4. Top: H NMR of cinnamylidene malonic acid. -
Bottom: 1H NMR of crystalline product after 200 minutes of
irradiation at 250 nm.
By examination of the molecular packing in the crystal
structure and comparing it to the photoproducts it is easy to see
that the head-to-tail relationship and inversion symmetry of the
crystal structure were retained in the product. The close
proximity and parallel relationship of reacting C5=C6 bonds
which is necessary for solid-state reactivity are also easily
observed. Bond formation can occur at either the top or bottom
face of the C5=C6 bonds since nearest neighbors are within the
4.2Å limit.
Figure 6. Kinetic study of 2+2 dimerization of cinnamylidene
malonic acid at 250 nm. a) The infrared bands used in the kinetic
study monomer (716 cm-1) and dimer (700 cm-1). b) Monomer/dimer
concentration vs. time. c) Straight line plot of ln(xmonomer) vs. time
indicating a 1st order reaction.
A modified Beers law method described by Matsomoto et.al. was
used to calculate the mole fraction of monomer and dimer during
the course of the reaction.8c Monomer concentration C1 can be
evaluated according to the following formula:
The infrared data indicated that the reaction proceeded to 85%
completion. A plot of the natural log of monomer vs. time was
consistent with a first order reaction which is consistent for
lattice controlled reactions (Fig. 6).
Conclusion
In summary, cinnamylidene malonic acid was synthesized and
its crystal structure determined. It was discovered that the
crystals underwent a photo-induced topochemical 2+2 reaction
which proceeded in 85% yield. The structure of the product was
determined by 1H and 13C NMR and its regio- and
stereochemistry were rationalized by examining the crystal
structure. Reactant molecules were arranged in a head-to-tail
fashion and related to nearest neighbors by inversion symmetry.
Reaction occurred between parallel C=C bonds that were in close
contact in the crystal structure. The head-to-tail relationship and
inversion symmetry were retained in the product. An infrared
kinetic study demonstrated pseudo first order kinetics. All of the
data taken together indicates that the 2+2 cycloaddition occurred
by a lattice controlled mechanism.
Figure 5. Molecular packing of nearest neighbors showing the head-
to-tail orientation of ║ alkenes. a) Geometric parameter d and θ2. b)
Illustration showing θ3.
Table 1. Intramolecular distances and angles reacting π
bonds.
approach
d C=C (Å)
θ2
θ3
top
bottom
3.597
3.689
109.19
98.33
76.27
73.41
reacting atoms are separated by 3.597Å on one face of the C=C
unit and 3.689Å on the other. It was not possible to determine
which mode of reaction is taking place since both lead to the
same product and both modes fall within the necessary
parameters for dimerization (Table 1, Fig. 5). However, both

4
Tetrahedron
Acknowledgments
We would like to acknowledge the Department of Chemistry
and Physics and the Graduate School of Western Carolina
University for providing funding for this research. We would
also like to thank the Department of Chemistry at the College of
William and Mary for providing access to their single crystal
diffractometer.
References and notes
1.
2.
3.
Ramamurthy, V.; Venkatesan, K.; Guru Row, T.N.; Swamy, H.R.;
Rao, C.N.N. Tett. Lett. 1983, V.24, No.31, 3262-3266.
a) Cohen, M. D. Angew. Chem.1975,87, 439. b) Ramamurthy, K.
Venkatesan, Chem. Rev., 1987, 87, 433-481.
a) Cohen, M. D.; Schmidt, G. M. J. J. Chem. Soc. 1964, 1996. b)
Cohen, M. D.; Schmidt, G. M. J.; Sonntag, F. I. J. Chem. Soc.
1964, 2000-2013. c) Cohen, M. D.; Schmidt, G. M. J. J. Chem.
Soc. 1964, 1996-2000.
4.
5.
6.
a) Venkatesan, K.; Ramamurthy, V; J. Org. Chem. 1985,50,
2337-2346. b) Yang, S. Y.; Naumov, P.; Fukuzumi, S..J.Am.
Chem. Soc. 2009,131, 7247−7249.
a) Cohen,M.D. Angew. Chem. Int. Ed. Engl., 1975, 14(6), 386. b)
Ramamurthy, V.; Weiss, R.G.; Hammond, G.S. Acc. Chem. Res.,
1993, 26, 530-536.
a) Zimmerman, H. E.; Nesterov, E. E.Acc. Chem. Res. 2002, 35,
77–85. c) Ramamurty,,U; Desirajua, G.R. IUCrJ 2015. 2, 653–
660.
7.
8.
a) I. Turowska-Tyrk, I. Chemical Physics Letters, 2002, 361,115–
120. b) Dunitz, J.D. Acta Cryst. (1995) B51, 619-631.
a) Turowska-Tyrk. J. Phys. Org. Chem. 2004, 17, 837–847. b)
Hasegawa, M; Shiba, S. J. Phys. Chem. 1982, 86, 1490-1492. c)
Matsumoto, A.; Tanaka, T.; Tsubouchi, T.; Tashiro, K.; Saragai,
S.; Nakamoto, S. J. Am. Chem. Soc. 2002, 124, 8891-8902.
Hoogen, N.; Oskar Nuyken, O. J. Poly Chem. Part A. 2000, 38,
1903–1910.
9.
10. CCDC identifier: 1553704. The crystals are monoclinic with the
space group P21/c. At 100 K, a = 6.9763(2), b = 10.4935(2), c =
13.8570(3) Å with β = 96.9330(10), V = 1007.00(4) Å3 and Z = 4.
11. Luigi D’Ascenzo, L.; Auffinger, P. Acta Cryst. 2015. B71, 164–
175.
12. Enkelmann, V; Wegner, G.. J. Am. Chem. Soc. 1993,115, 10390-
10391.

5

6
Tetrahedron

7

8
Tetrahedron

9

10
Tetrahedron

11

12
Tetrahedron
The crystal structure of cinnamylidene
malonic acid was obtained and it was found
to undergo 2+2 dimerization upon
irradiation at 250nm.
 The structure of the photoproduct was
determined by 1H and C13 NMR.
 The head-to-tail relationship and inversion
symmetry relating reactants in the crystal
were retained in the product.
 A kinetic study demonstrated pseudo first
order kinetics which is consistent with a
solid state reaction which is under lattice
control.