Regioselective photoreactions within a series of mixed co-crystals containing isosteric dihalogenated resorcinols with 4-stilbazole

Article abstract of DOI:10.1039/c9pp00004f

The formation and photoreactivity of a series of mixed co-crystals containing 4-stilbazole along with both 4,6-dichlororesorcinol and 4,6-dibromoresorcinol at various ratios is reported. In all cases, the quantitative [2 + 2] cycloaddition reaction yields

Full text of DOI:10.1039/c9pp00004f

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Regioselective photoreactions within a series
of mixed co-crystals containing isosteric
Cite this: DOI: 10.1039/c9pp00004f
dihalogenated resorcinols with 4-stilbazole†
Received 2nd January 2019,
Accepted 27th February 2019
Anna L. Grobelny,a Nigam P. Rathb and Ryan H. Groeneman
*
a
DOI: 10.1039/c9pp00004f
rsc.li/pps
The formation and photoreactivity of a series of mixed co-crystals workers where they reported the photochemical reactivity of a
containing 4-stilbazole along with both 4,6-dichlororesorcinol and solid solution containing 3-chloro-trans-cinnamic acid and
4,6-dibromoresorcinol at various ratios is reported. In all cases, the 3-bromo-trans-cinnamic acid which undergoes a solid-state
quantitative [2 + 2] cycloaddition reaction yields an identical head- [2 + 2] cycloaddition reaction.6 Since the crystal was a solid solu-
to-tail photoproduct, namely rctt-1,3-bis(4-pyridyl)-2,4-bis tion, three photoproducts were realized, namely 3,3′-dichloro-
(phenyl)cyclobutane. The selectivity in the cycloaddition reaction β-truxinic acid, 3,3′-dibromo-β-truxinic acid, and 3-bromo-3′-
occurred due to
a shorter distance observed between two chloro-β-truxinic acid, resulting in two homodimers and one
carbon–carbon double bonds that were found between and not heterodimer for the latter. In a template-based approach,
within the hydrogen-bonded assemblies.
MacGillivray and co-workers reported the ability to achieve a
cross-photodimerization reaction within a hydrogen-bonded
solid based upon resorcinol (res) with two isosteric reactants,
Mixed co-crystals (i.e. co-crystal solid solutions) have remained
an understudied area of crystal engineering even though there
are documented applications in the area of pharmaceuticals1
and inclusion chemistry.2 The solid-state photochemistry, in
particular the [2 + 2] cycloaddition reaction, of these solid
solutions and mixed co-crystals has received even less atten-
tion in the chemical literature. In contrast, the number of
papers that discuss the photoreactivity of single- and multi-
component molecular solids continues to indicate that it is
still an active area of research.3
namely
trans-1-(4-chlorophenyl)-2-(4-pyridyl)ethylene
and
trans-1-(4-methylphenyl)-2-(4-pyridyl)ethylene.7 A cross photo-
product was achieved due to the similar size of the chloro and
methyl groups on the reactant molecules and their ability to
easily substitute for each other in the crystal lattice resulting in
a co-crystal solid solution. After exposure to UV light the for-
mation of both homodimers and heterodimers of the cyclo-
butane-based photoproducts was realized.
Recently, we reported the ability to control the regio-
chemistry of the resulting photoproduct by varying the
halogen atoms on two isosteric resorcinol templates, namely
4,6-dichlororesorcinol (4,6-diCl res) and 4,6-dibromoresorcinol
(4,6-diBr res) with 4-stilbazole (4-SB).8 The reactant molecule 4-
SB can yield two regioisomers for the photoproduct due to its
unsymmetrical nature. In particular, the isostructural co-crys-
tals (4,6-diCl res)·2(4-SB) and (4,6-diBr res)·2(4-SB) yielded
either a head-to-tail (ht) or head-to-head (hh) photoproduct,
respectively (Scheme 1). The observed change in the regio-
chemistry was attributed to the differences in the carbon–
carbon double bond (CvC) distances within or between hydro-
gen-bonded assemblies. Due to the isostructural nature of the
crystals and the fact that the two dihalogenated-res templates
are isosteric makes this an ideal case to investigate the photo-
chemistry and the resulting regiochemistry of the photopro-
duct as a mixed co-crystal. In this paper, we will discuss
the formation, structure, and preferred photoproduct from
a series of mixed co-crystals based upon varying the amounts
Solid solutions and mixed co-crystals are different from
multicomponent molecular solids,4 since the location of
similar shaped molecules can vary throughout the crystal
lattice.5 In particular, a mixed co-crystal is formed when two or
more isosteric molecules crystallize where there is a shared
and common component. In these cases, the mixed co-crystal
forms since these isosteric molecules can readily replace each
other at equivalent crystallographic positions. One example of
a photoreactive solid solution was reported by Harris and co-
aDepartment of Biological Sciences, Webster University, 470 East Lockwood Ave.,
St. Louis, MO 63119, USA. E-mail: ryangroeneman19@webster.edu;
Tel: +1 314-246-7466
bDepartment of Chemistry and Biochemistry and the Center for Nanoscience,
University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA
†Electronic supplementary information (ESI) available: Experimental details,
single crystal and powder X-ray data, and 1H NMR spectra. CCDC
1867907–1867910. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c9pp00004f
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Table 2 Hydrogen bond distances and olefin–olefin distances (cen-
troid–centroid) for the various mixed co-crystals
Initial percent (Cl/Br)
O–H⋯N hydrogen bond
distances (Å)
25/75
2.688(2)
2.695(2)
50/50
75/25
2.690(2)
2.690(2)
4.31
2.670(5)
2.681(5)
4.29
Olefin–olefin distance within 4.32
the assembly (Å)
Olefin–olefin distance
4.02
4.04
4.04
between assemblies (Å)
Scheme 1 The observed photoproducts for the pure co-crystals (4,6-
diCl res)·2(4-SB) and (4,6-diBr res)·2(4-SB) and the mixed co-crystal
(4,6-diCl/Br res)·2(4-SB).
of the two res-based templates along with 4-SB as the reactant.
Surprisingly, the head-to-tail photoproduct was the only regio-
isomer realized in the different mixed co-crystals regardless of
the ratios of the res-templates.
Three mixed co-crystals were prepared at various percen-
tages, namely 25/75, 50/50, and 75/25 for 4,6-diCl res and 4,6-
diBr res, respectively.‡ To form different mixed co-crystals, the
amount of 4-SB was constant at 25 mg and was dissolved in
2 mL of ethanol in a scintillation vial. Each of the res tem-
plates was then dissolved in 1 mL of ethanol and then the
three corresponding solutions were combined after all of the
solids dissolved. The three combined solutions were all
allowed to slowly evaporate under ambient conditions. Crystals
suitable for X-ray diffraction formed within three days in each
case. X-ray diffraction data determined the overall formula for
Fig. 1 X-ray crystal structure of the stacked three-component hydro-
gen-bonded assemblies of (4,6-diCl/Br res)·2(4-SB).
each mixed co-crystal and in all cases a general formula of (Fig. 1). In all structures, the quadruple stack of 4-SB mole-
(4,6-diCl/Br res)·2(4-SB) was realized (Table 1).§
cules is capped with a pair of res-based templates at both
The diffraction data determined that each mixed co-crystal ends. The distance between a pair of CvC bonds varies based
ˉ
crystallized in the centrosymmetric triclinic space group P1 upon the percent of each res template and if it occurs within
with similar crystallographic parameters (Table 1). All of the or between hydrogen-bonded assemblies (Table 2). The short-
mixed co-crystals are isostructural and are based upon a three- est CvC bond distances were observed between hydrogen-
component assembly held together by two O–H⋯N hydrogen bonded assemblies with values ranging from 4.02 to 4.04 Å.
bonds (Tables 1 and 2). Each asymmetric unit contains one The distances within the hydrogen-bonded assemblies were
template molecule along with two unique 4-SB molecules. larger with values ranging between 4.29 and 4.32 Å. Powder
There was no disorder of the ethylene core on any of the 4-SB X-ray diffraction was employed to confirm the structure of the
molecules at 290 K. Similar to the previously reported structure bulk material as compared to the single crystal structure. In all
of the pure co-crystals, each mixed co-crystal contains a quad- three cases, the bulk diffractogram matches the calculated
ruple stacking of 4-SB molecules where the nearest neighbor- pattern from the observed single crystal structure (Fig. S1–S3†).
ing hydrogen-bonded assemblies are again found to be anti In addition, the powder patterns of the various mixed co-
Table 1 Selected crystallographic parameters and occupancies for the various mixed co-crystals
Initial percent (Cl/Br)
Experimental percent (Cl/Br)
25/75
38/62
50/50
50/50
75/25
67/33
Experimental formula
a (Å)
b (Å)
c (Å)
C32H26Br1.24Cl.76N2O2
10.9822
10.9866
11.6040
98.151
C32H26BrClN2O2
10.9647
11.0160
11.6107
91.273
C32H26Br.66Cl1.34N2O2
10.9120
10.9997
11.6021
91.680
α (°)
β (°)
90.796
91.779
1385.1
97.696
91.769
1388.6
97.459
91.733
1379.4
γ (°)
Volume (Å3)
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crystals matched indicating that the ratio or amount of each tant molecules must photoreact with a 4-SB molecule from a
res template does not significantly alter the crystal structure. neighboring assembly to achieve the overall quantitative yield.
The resulting solids of each mixed co-crystal were placed A powder X-ray diffraction experiment after the photoreaction
between glass plates and placed in a photoreactor cabinet to indicates a change in the solid-state structure when compared
determine if a solid-state [2 + 2] cycloaddition reaction would to the single-crystal data before irradiation (Fig. S4†). The
occur. The samples were exposed to broadband UV radiation photoreaction is believed to occur in the solid state and not in
from a 450 W medium-pressure mercury lamp. Surprisingly, a melt, since (4,6-diCl/Br res)·2(4-SB) has a melting point of
identical photoproducts were observed for all mixed co-crystals 131 °C which is significantly higher than the temperature
as evidenced by the appearance, in particular the shape and within the photoreactor (ca. 32 °C)9 after four hours of
width, of the cyclobutane peak at 4.58 ppm in the 1H NMR irradiation. Lastly, due to this substantial difference in temp-
spectrum (Fig. S5–S7†). In all solids, a quantitative yield for erature the outer 4-SB molecules must move in some coopera-
the cycloaddition reaction was achieved within 20 hours of tive manner in the solid state to position the remaining CvC
irradiation which is equal to the length of time for each pure bonds in the correct orientation to react and reach the
co-crystal.8 In all three mixed co-crystals, the photoreaction did observed quantitative yield.
not proceed via a single-crystal-to-single-crystal transform-
ation, since within the first 4 hours of UV exposure, crystal-
linity was lost.
Conclusions
As previously reported, the shape and width of the cyclo-
In this Communication, we reported a regioselective photo-
reaction within a series of mixed co-crystals with a general
formula of (4,6-diCl/Br res)·2(4-SB) where in all cases only the
ht-PP was observed. This was an excellent case to investigate
the photochemical properties of this system, since the two
pure co-crystals were isostructural and were based upon isos-
teric template molecules resulting in different regioisomers of
the photoproduct. Currently, we are trying to increase the
number of unique molecules in this mixed co-crystal by the
addition of similar shaped components to this structure.
butane peak indicate that the photoproduct is the head-to-tail
regioisomer, namely rctt-1,3-bis(4-pyridyl)-2,4-bis(phenyl)cyclo-
butane (ht-PP).8 In order to confirm this assignment of regio-
chemistry, the photoproduct from the 50/50 mixture was
recrystallized from 3 mL of ethanol. Within two days crystals
suitable for X-ray diffraction formed via slow evaporation of
the solvent. X-ray diffraction analysis determined that the
photoproduct contained a mixed co-crystal with a general
formula of (4,6-diCl/Br res)·(ht-PP). As in the pure co-crystal
(4,6-diCl res)·(ht-PP), the mixed co-crystal was found to crystal-
lize in the noncentrosymmetric orthorhombic space group
Pna21 where the solid is held together by two O–H⋯N hydro-
gen bonds [O⋯N (Å): 2.714(3) and 2.773(3)]. As a result of the
divergent nature of ht-PP again a helical one-dimensional
hydrogen-bonded polymer was achieved (Fig. 2). The free vari-
able refinement of the halogen atoms in the mounted mixed
co-crystal determined the percentages to be 40/60 for 4,6-diCl
res/4,6-diBr res, respectively.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
Interestedly, only one photoproduct was observed in all
mixed co-crystals based upon the shorter CvC bond distances
between the hydrogen-bonded assemblies rather than within
the assembly. As reported in the pure co-crystals, there is again
a quadruple stack of reactant 4-SB molecules in the various
mixed co-crystals.8 As in (4,6-diCl res)·2(4-SB), the middle pair
of 4-SB photoreacts to form the ht-PP while the outer two reac-
R. H. G. gratefully acknowledges financial support from
Webster University from both Faculty Research Grants and
Faculty Development Fund.
Notes and references
‡The initial percent of (4,6-diCl res) and (4,6-diBr res) within each mixed co-
crystal was based upon the stoichiometric amounts used in the co-crystallization
process.
§The experimental percent of (4,6-diCl res) and (4,6-diBr res) within each mixed
co-crystal was determined from diffraction data by using free variable refine-
ments to obtain the relative ratio of each component.
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