Dewar benzene as a protecting group? demonstration of photolithographic crystallization

Article abstract of DOI:10.1021/ol0166810

The concept of Dewar benzene as a supramolecular protecting group for solid-state aryl-aryl interactions is reported. Photoisomerization of 1,4,5,6-tetramethyl-bicyclo[2.2.0]hexa-2,5-diene-2,3-dicarboxylic acid dimethyl ester (1) to the corresponding benzene isomer proceeds with rapid crystal formation. Herein this property is applied to the photolithographic patterning of crystal domains on a surface.

Full text of DOI:10.1021/ol0166810

ORGANIC
LETTERS
2001
Vol. 3, No. 24
3847-3849
Dewar Benzene as a Protecting Group?
Demonstration of Photolithographic
Crystallization
Michael J. Marsella,* Mathew M. Meyer, and Fook S. Tham
Department of Chemistry, UniVersity of California at RiVerside,
RiVerside, California 92521-0403
michael.marsella@ucr.edu
Received August 31, 2001
ABSTRACT
The concept of Dewar benzene as a supramolecular protecting group for solid-state aryl−aryl interactions is reported. Photoisomerization of
1,4,5,6-tetramethyl-bicyclo[2.2.0]hexa-2,5-diene-2,3-dicarboxylic acid dimethyl ester (1) to the corresponding benzene isomer proceeds with
rapid crystal formation. Herein this property is applied to the photolithographic patterning of crystal domains on a surface.
Although protecting groups play a crucial role in covalent
synthetic chemistry,1,2 their role in supramolecular chemistry
is practically nonexistent. In theory, supramolecular protect-
ing groups could contribute significantly to fields such as
crystal engineering,3,4 providing a means to diminish specific,
noncovalent, intermolecular interactions, thus biasing self-
assembly by design. With regard to crystal engineering, such
protecting groups must be the epitome of atom economy.5
Specifically, deprotection must not require or produce any
unwanted chemical species, as they would ultimately con-
stitute impurities within the crystal lattice. Such restrictions
are significant and limit the use of most common protecting
groups. Herein we propose Dewar benzene as a supra-
molecular protecting group for aryl-aryl supramolecular
interactions and exemplify its use by demonstrating photo-
lithographic patterning of crystal domains on a surface.
The ideal supramolecular protecting group is subject to
several requirements. As stated, it cannot require or produce
unwanted chemical species. Furthermore, conversions must
be quantitative and irreversible. Finally, the protecting group
must be capable of masking all intrinsic properties of the
parent synthon that would otherwise lead to noncovalent
interactions (hence its denotation as a protecting group). To
test this concept, we have employed the photochemical
conversion of Dewar benzene to benzene. Our choice was
based, in part, on the ability of the Dewar isomer to
completely destroy all aspects of aromaticity, hence muting
the ubiquitous supramolecular aryl-aryl interaction.
During the course of investigating a series of Dewar
benzenes, we recognized that the known Dewar benzene,
compound 1,6 underwent a photoisomerization and com-
mensurate phase change, converting from an oil (compound
1) to a crystalline solid (compound 2). We recognized that
this observation may serve as a highly visual litmus test of
the aforementioned concept, Dewar benzene as a protecting
group. Substantiation of such a claim would require not only
meeting the aforementioned requirements but also clear
demonstration of aryl-aryl interactions in the X-ray crystal
structure of compound 2.
(1) Green, T. W. ProtectiVe Groups in Organic Synthesis; Wiley: New
York, 1980.
(2) Wuts, P. G. M.; Green, T. W. ProtectiVe Groups in Organic Synthesis;
Wiley: New York, 1991; Vol. 2.
(3) Desiraju, G. R. Crystal Engineering. The Design of Organic Solids;
Elsevier: New York, 1989; Vol. 54.
The Koster procedure was implemented for the synthesis
of Dewar benzene 1 (Scheme 1)6 By streamlining the
(4) Desiraju, G. R. Angew. Chem., Int. Ed. Engl. 1995, 34, 2311-2327.
(5) Trost, B. M. Science 1991, 254, 1471.
(6) Koster, J. B.; Timmermans, G. J.; van Bekkum, H. Synthesis 1971,
139-140.
10.1021/ol0166810 CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/30/2001

Given the aforementioned results, Dewar benzene 1 is an
ideal example of a supramolecular protecting group for
synthon 2. Specifically, the protecting group eradicates the
aryl moiety, thus inhibiting intermolecular aryl-aryl inter-
actions that would otherwise promote crystallization. De-
protection via photoisomerization is quantitative, irreversible,
and without byproduct, and subsequent crystal formation
takes place spontaneously. Furthermore, the thermal stability
of compound 1 at room temperature is excellent (complete
thermal isomerization requires heating in refluxing toluene
for ca. 2 h).11 Last, the X-ray crystal structure of compound
2 reveals a face-to-face packing motif exhibiting a neighbor-
ing aromatic ring C‚‚‚C spacing of 3.780 Å (Figure 1).12
Such a packing motif is characteristic of the aryl-aryl
supramolecular synthon.3,4,8
Scheme 1
reported workup, we were able to increase isolated yields
of compound 1 from 27% to 44%. Regardless, partial
isomerization of reactive 1 typically takes place during the
course of the reaction and/or workup, thus contaminating
isolated product with trace amounts of compound 2. Fortu-
nately, this mixture can be readily separated by addition of
pentane and subsequent filtration, as the two isomers have
dramatically different solubilities. Indeed, contamination of
1 by 2 is detected by the presence of a heterogeneous mixture
of needle-shaped crystals (2) and oil (1). Note that the neat
mixture does not prevent crystallization of the minor
component. Isolated crystals of compound 2 exhibit a melting
point of 128 °C. The latter two facts illustrate that the strong
crystal packing forces present in compound 2 are muted in
isomer 1.
The difference in propensity for the two isomers to
crystallize stems, in part, from their topological differences.
Scheme 1 shows the side-on view of the two isomers (space
filling models; minimized at the PM3 level of theory7). Note,
however, that topology is not the only factor driving aryl-
aryl interactions.3,4,8 As stated, a protecting group for aryl-
aryl interactions must eradicate all intrinsic properties of the
aryl moiety, hence our choice of Dewar benzene.
When neat samples of 1 are irradiated with 365 nm light,
photoisomerization is followed by rapid crystal formation.
The efficiency of this process is remarkable and led us to
believe that the conversion from 1 to 2 takes place with the
absence of byproducts. Monitoring this process by 1H NMR
confirmed that the photoisomerization was indeed quantita-
tive.9 In contrast to this result, it should be noted that
examples of product mixtures resulting from the photoirra-
diation of Dewar benzenes have been reported.10
Figure 1. ORTEP representations of compound 2 viewed (a) down
and (b) along the face-to-face stacks. The closest C‚‚‚C aromatic
ring distance in this face-to-face packing motif is 3.780 Å.
(7) Calculations reported herein were performed using Titan software,
Schro¨dinger, Inc., 1500 SW First Avenue, Suite 1180, Portland, OR 97201.
(8) Desiraju, G. R.; Gavezzotti, A. J. Chem. Soc., Chem. Commun. 1989,
621-623.
3848
Org. Lett., Vol. 3, No. 24, 2001

In an effort to provide a visual litmus test of this concept,
we focused on the application of photolithographic patterning
of crystal domains on a surface. In theory, such an application
may add a significant processing tool to the field of crystal
engineering. The following conditions represent our initial
(unoptimized) efforts to perform photolithographic crystal-
lization using compound 1.
A neat sample (ca. 10 µL) of compound 1 (oil) was
sandwiched between two 1” × 3” standard microscope slides.
A shadow mask was prepared by ink-jet printing a design
onto a transparency film and was subsequently affixed to
the exterior surface of the top microscope slide. The sample
was irradiated for 15-20 min at 25 °C (365 nm @ 7
mW/cm2). If crystals were not immediately apparent, the
sample was cooled to 0° until the formation of colorless
crystals within the unmasked area was detected by the naked
eye. This latter process took place rapidly. To best assess
the match between mask design and crystal domain, the
sample was examined under a cross-polarizing microscope.
Under these viewing conditions, regions of amorphous 1
appear dark (denoting the protected region), while crystals
of 2 are readily visible (denoting that deprotection has
occurred; see Figure 2). As a litmus test for our proposed
concept, it is visually apparent from Figures 1 and 2 that
aryl-aryl interactions are, as expected, activated (depro-
tected) by photoisomerization. Furthermore, given the sim-
plicity of the unoptimized photolithographic conditions, the
match between mask and crystal domain is excellent (Figure
2; both mask and crystal domains have dimensions of 1.05
cm × 0.45 cm).
Figure 2. (a) Photograph showing the patterned crystal domain
of compound 2 surrounded by amorphous compound 1 (light and
dark areas, respectively, as viewed under cross polarizers). (b)
Magnified view of the top left corner of patterned crystal domain
shown in (a).
corresponding supramolecular protecting group and high-
lighted such an application by demonstrating a process we
have termed “photolithographic crystallization.” In an effort
to further test the scope of this supramolecular protecting
group, we are currently investigating synthetic methodology
aimed at facilitating the covalent incorporation of Dewar
benzene moieties onto a wide range of molecular scaffolds.
Aryl-aryl interactions are a ubiquitous supramolecular
synthon, playing a dominant role in many self-assembly
processes. Herein, we have proposed Dewar benzene as the
Acknowledgment. This work was supported by the
National Science Foundation (CHE-9974548), DuPont (Young
Professor Grant to M.J.M.), and the University of California.
(9) Characterization of compounds 1and 2 are consistent with literature
values. Compound 1: see ref 6. Compound 2, see: McAlister, D. R.;
Bercaw, J. E.; Bergman, R. G. J. Am. Chem. Soc. 1977, 99, 1666-1668.
(10) Gleiter, R.; Treptow, B. J. Org. Chem. 1993, 58, 7740-7750.
(11) Gleiter, R.; Ohlbach, F.; Oeser, T.; Irngartinger, H. Liebigs Ann.
1996, 785-790.
Supporting Information Available: Details of X-ray
determination. This material is available free of charge via
the Internet at http://pubs.acs.org.
(12) Crystallographic data has been deposited in the Cambridge Crystal-
lographic Data Centre Database.
OL0166810
Org. Lett., Vol. 3, No. 24, 2001
3849