Organic Molecules with Porous Crystal StructuresOrganic Molecules with Porous Crystal Structures
Mohamed I. Hashim Chia-Wei Hsu Ha T. M. Le Ognjen Š. Miljanić*
University of Houston, Department of Chemistry, 3585 Cullen Boulevard #112, Houston TX 77204-5003, [email protected]
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Received: 19.02.2016Accepted after revision: 24.03.2016Published online: 18.05.2016DOI: 10.1055/s-0035-1561448; Art ID: st-2016-a0120-a
Abstract Porous materials have numerous applications of relevance toenergy, the environment, and catalysis. A relatively recent addition tothe field are porous molecular crystals, whose solid-state structurescontain discrete molecules held together only by weak noncovalentforces. This contribution summarizes recent developments in the area,before providing an account of our own adventures in the field whichare centered on the creation of robust fluorinated porous molecularcrystals. We will also present the recent discovery of a one-step synthe-sis of a new class of macrocycles dubbed cyclobenzoins; an example isgiven of such a shape-persistent structure that translates into mild po-rosity in the solid state.1 Introduction2 Early Days3 Intrinsically Porous Molecular Crystals4 Extrinsically Porous Molecular Crystals5 Fluorinated Porous Molecular Crystals6 Cyclobenzoins: Shape-Persistent and Intrinsically Porous?7 Conclusions
Key words porosity, molecular crystals, fluorocarbons, benzoin con-densation, shape-persistent macrocycles
1 Introduction
Porous materials have a plethora of applications in ener-gy-related industries.1 In an excellent and very approach-able recent review, Slater and Cooper divided the currentlyknown porous materials into five categories: zeolites, met-al–organic frameworks (MOFs), covalent organic frame-works (COFs), porous organic polymers, and porous molec-ular solids.2 Zeolites are fully inorganic and highly crystal-line structures; MOFs are crystalline inorganic/organichybrids, wherein organic struts connect metal clusternodes in an infinite structure. The last three classes of po-
rous materials are typically fully organic: COFs are general-ly microcrystalline3 and porous organic polymers amor-phous, while porous molecular solids can often be manu-factured into crystals suitable for analysis by single-crystalX-ray diffraction.
The first four classes are polymeric materials, meaningthat they are generally impossible to dissolve without de-composition. In contrast, porous molecular crystals arecomposed of discrete molecules that pack in the solid statein a manner that leaves large voids. This distinction makesporous molecular crystals unique among other porousstructures. They are generally solution-processable and assuch the mechanism of their assembly and function can bestudied using well-established solution-phase spectroscop-ic tools. In addition, the fact that there are no strong cova-lent bonds holding individual molecules together makesthese crystals ‘rubbery’, as the distances between the mole-cules can change even in the solid state. This feature is rele-vant, for example, in the motion and transport of gueststhrough the pores, as well as in guest sensing.
Porous molecular crystals are a rare beast though. Mole-cules prefer to closely pack in the solid state because of en-tropic considerations, as well as to maximize attractive in-termolecular contacts; thus, structures that leave largevoids are not common. Even in cases where voids are ob-served in the crystal structure, they are typically filled withdisordered solvent molecules. Upon solvent removal, thesestructures tend to collapse as the noncovalent bonds be-tween individual molecular building blocks are weak.
Porous molecular crystals can be divided into two cate-gories: intrinsically and extrinsically porous.4 The formerare composed of individual molecules which bring theirown porosity into the crystal by having a large, shape-per-sistent void; molecular cages and macrocycles fall into thiscategory. Extrinsically porous crystals are formed from
molecules that have no void, but whose inefficient packingin the solid state leaves large empty spaces. In other words,in intrinsically porous crystals, molecules bring their poros-ity with them; with extrinsically porous ones, porosity is afeature of crystal packing. Combinations of the two catego-ries are possible as well.
We got ourselves into the chemistry of porous molecu-lar crystals by pure accident. This account will describe that
accident and the somewhat less accidental studies that fol-lowed, but will begin with a survey of the work of some ofour colleagues worldwide which continues to inspire us.We have not strived for a comprehensive review of the field,but instead present a personal perspective complementaryto several reviews of porous molecular crystals which havebeen published already.4–7 We will focus on all-organic andcrystalline systems, thus excluding other discrete porous
Biographical Sketches
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Mohamed I. Hashim gradu-ated from the United Arab Emir-ates University in 2006 with aB.S. degree in chemistry. Hethen went on to earn an M.S.
degree in chemistry from theUniversity of Texas–Pan Ameri-can in 2010, where he conduct-ed research under the tutelageof Professor Bimal K. Banik. Cur-
rently he is a Ph.D. candidate inthe group of Professor OgnjenMiljanić at the University ofHouston (UH).
Chia-Wei Hsu is from Tainanin Taiwan. Between 2004 and2008, he earned his B.S. andM.S. degrees at the National Ts-ing Hua University (NTHU) inTaiwan. At NTHU, he performedresearch under the supervision
of Dr. Yi-Chou Tsai, focusing onthe synthesis and characteriza-tion of complexes with metal–metal multiple bonds. In 2011,he joined Dr. Miljanić’s group atUH, where he is currently aPh.D. candidate, working in the
area of physical organic chemis-try. He was a recipient of theOutstanding Teaching Award(2013) and Graduate ResearchAward (2015) given by the UHDepartment of Chemistry.
Ha T. M. Le obtained her B.S.degree in chemical engineeringfrom the Ho Chi Minh City Uni-versity of Technology in Viet-nam in 2010 and her Ph.D. in
chemistry from UH in 2015,where she worked under the su-pervision of Professor OgnjenMiljanić. She is currently a post-doctoral researcher at UH. Her
research focuses on the synthe-sis and characterization of fluo-rescent sensors andnoncovalent organic frame-works.
Ognjen Š. Miljanić was bornin Belgrade, then Yugoslavia, in1978. He holds a diploma(2000) from the University ofBelgrade and a Ph.D. (2005)from the University of California
at Berkeley. Between 2005 and2008, he was a postdoctoralscholar at the University of Cali-fornia, Los Angeles. He startedhis independent career at UH in2008, where he is presently As-
sociate Professor of Chemistry.He was a 2013 Cottrell Scholarand a recipient of the NSF (Na-tional Science Foundation) CA-REER and UH Research andTeaching Excellence awards.
Many organic compounds have apparent pores in theirsolid-state structures. Normally, these pores are filed withmolecules of a disordered solvent left over from synthesis.In some cases of well-defined inclusion compounds, guestsother than solvent molecules can be found in a more or lessordered orientation within the pores. In the vast majority ofcases, these pores collapse as the included guests are re-moved; the reasons for this are thermodynamic as the morestable close-packed structure (with included guests) givesrise to the less stable structure with voids. Here, we will fo-cus on the systems that resist structural collapse upon sol-vent (or guest) removal and are conventionally porous. For aseries of cautionary notes, the reader is referred to Barbour’scritical discussion7 of ‘virtual porosity’ often claimed in theliterature.
Dianin’s compound 1 (Figure 1), first reported in 1914,9was among the earliest examples shown to sorb a series ofgases despite the absence of large-enough apertures in thecrystal structure through which such gases could pass.10
This intriguing behavior, dubbed ‘porosity without pores’,has been observed in other molecules, including calixarene2,11 and has been explained as occurring through dynamiccooperativity allowing guest transport into the interior ofthe crystal.
Figure 1 Selection of organic compounds with porous solid-state structures, reported prior to 2011
Tris(o-phenylenedioxy)cyclotriphosphazene (TPP, 3)(Figure 1) has been shown to be porous and adsorb CO2,CH4, and several other gases within its hexagonal pores.12
Several simple hydrophobic dipeptides have also beenfound to organize into porous structures in the solid state.13
These include L-alanyl-L-valine and L-valyl-L-alanine,14 aswell as a few other dipeptides of lower porosity.15
Shimizu’s group at the University of South Carolina re-ported the synthesis of porous bis-urea 4 (Figure 1) in2003.16 This compound was organized into columnar stacksmediated by hydrogen-bonded ‘tapes’ between urea moi-eties. It was found to reversibly adsorb AcOH, and itsBrunauer, Emmett, and Teller (BET) surface area was 316m2·g–1.17 In a subsequent study, the same group reportedtetrayne-based macrocycle 5 with a BET surface area of~350 m2·g–1 which was shown to topochemically polymer-ize upon heating.18 Shimizu’s work in this area was recentlyreviewed.19 In 2013, a large number of isostructural and ex-trinsically nanoporous steroidal tris-ureas was reported aswell.20
In 2009, McKeown reported the crystal structure of bi-phenyl-based tetrayne 6 (Figure 2), which was found tocrystallize in a porous arrangement.21 Interestingly, thisstructure was not designed and then synthesized, but wasinstead discovered in the Cambridge Structural Database byfollowing a set of criteria that McKeown proposed as usefulin searching for porous structures. These include: (a) crystaldensity lower than 0.9 g·cm–3, (b) crystal composed of rigidaromatic molecules, and (c) small pore sizes. The BET sur-face area of 6 was characterized as 278 m2·g–1. The crystalstructure seemed to be stabilized mostly by [C–H···π] inter-actions and to additionally profit from the bicontinuousmicroporous surface of the crystal which reduces sensitivi-ty to mechanical stress. Very recently, a computationalstudy analyzed a set of 150000 previously reported crystalstructures of organic molecules and identified 481 poten-tially porous organic molecular crystals.22 This result testi-fies both to the generality of this method of identificationof porosity and to the rarity of porous crystal structuresamong organic molecules.
1
N
N
N
OP
O
OP
O
O
PO
O
OH
N N
HH
O
N N
HH
O
O O
O
O
N
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H
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HO
HOOH
OH
2 3
4 5
Figure 2 Tetrayne 6 (left) that crystallizes as a porous structure, a seg-ment of which is shown (right) (element colors: Si—yellow, C—gray, H—white)
Porous Imine CapsulesIn a seminal 2009 paper, Cooper’s group at the Universi-
ty of Liverpool reported the synthesis of porous organiccages based on imine linkages.23,24 Tetrahedral cages 11–14were synthesized through a [4+6] cyclocondensation of1,3,5-triformylbenzene with four vicinal diamines: 1,2-eth-anediamine (7), 1,2-propanediamine (8), (R,R)-1,2-diami-nocyclohexane (9), and (R,R)-1,2-diaminocyclopentane (10)(Scheme 1).24,25 The BET surface areas of these cages werefound to be in the 500–600 m2·g–1 range, and the cageswere found to decompose only above 320 °C, as determinedby in-situ single-crystal X-ray diffraction analysis. The crys-tal porosity of these materials was attributed both to the in-trinsically porous cage structures and the inefficient pack-ing of tetrahedral cages.4
Scheme 1 Synthesis of porous imine cages 11–14 by Cooper’s group
The crystal packing and the topology of the porousstructures were strongly dependent on cage vertices de-rived from the alkyl groups on the diamine linker, whosesteric bulk led to pores that were either connected or isolat-ed (Figure 3). Cage 11 packs in a window-to-arene stack
with no intercage window connectivity; it is hence nonpo-rous but has isolated lattice voids (Figure 3, part A). Eventhough 12 has analogous packing to 11, owing to the sterichindrance of the methyl group over six vertices, cage 12features a one-dimensional undulating pore channel run-ning between the cages, but not connecting with the cagevoids (Figure 3, part B).23 On the other hand, cage 13 packsin a window-to-window arrangement as a result of inter-locking of cyclohexyl groups to produce an interconnectedthree-dimensional diamondoid homochiral pore network(Figure 3, part C).26
Figure 3 Differences in the crystal packing of porous imine cages 11–13
Cage 11 experiences morphology changes dependent onthe recrystallization solvent. Its porosity can be switchedon or off between three polymorphs: nonporous 11α (SABET= 23 m2 g−1), selectively porous to hydrogen 11β (SABET = 30m2 g−1), and highly porous 11γ (SABET = 550 m2 g−1). Switch-ing between the polymorphs is caused by three trigger or-ganic solvents. After its isolation from EtOAc and desolva-tion, nonporous 11α can be exposed to DCM to yield 11β, oro-xylene to form 11γ.24,26
Reduction of imine cage 11 into the correspondingamine was achieved in quantitative yield using NaBH4. Theresultant amine is an interesting twelve-arm building blockwhich could be functionalized, for example, by acylation toproduce a series of dodecaamide cages. The authors pro-posed it as a novel—and inherently porous—node in den-drimers, MOFs, and COFs.27 Cage 13 could be successfullydoped with vapors of OsO4; the crystal structure revealedthe presence of 2.5 molecules of OsO4 per cage. In the samestudy, Cooper and co-workers showed that doping of 13with iodine vapors resulted in the formation of I5
–@13+,wherein the oxidized cage acted as the counterion to the V-shaped pentaiodide.28
Cooper’s group also discovered that porous organic co-crystals can be made simply, and in a modular fashion, bycombining the above described cages in solution and thenslowly evaporating this solution. For example, evaporationof an equimolar solution of cages 11 and homochiral (R)-13
led to a quasiracemic cocrystal composed of (S)-11 and (R)-13. Cage 11 in the solid state is a mixture of two helicallychiral enantiomers (R)-11 and (S)-11, which rapidly inter-convert, allowing complete amplification of (S)-11 in thepresence of (R)-13. In the solid state, (S)-11 and (R)-13 al-ternate in a face-centered cubic ZnS crystal lattice, yieldingan overall porous cocrystal (SABET = 437 m2·g–1) as the twomodules orient in a window-to-window fashion.29 Impor-tantly, this work involved crystal structure prediction fromfirst principles. During the course of this study, anotherlarger imine-based cage was produced from tris(4-formyl-phenyl)amine and chiral (R,R)-1,2-cyclopentadiaminewhich had a BET surface area of 1333 m2·g–1.
In an extension of this strategy, Cooper’s group also dis-closed ternary porous cocrystals.30 In this ‘porous organicalloy’, 50% of the lattice positions are occupied by (S)-11,while the alternating positions are occupied by the disor-dered mixture of (R)-13 and (R)-14. In the alloy 11·13n·141–n,the ratio of 13 to 14 can be continuously varied betweenthe two binary cocrystal compositions, and the BET surfacearea increases almost linearly with the proportion of 14,from 373 (0% of 14) to 670 (50% of 14) m2·g–1.
Efforts to increase the size or change the geometry ofporous imine-based cages met with limited success. Cooperand co-workers reported propeller-shaped structure 15(Figure 4), which was synthesized in a one-step [2+3] cyclo-imination of 1,3,5-tris(4-formylphenyl)benzene with 1,5-pentanediamine. This new cage crystallized as a closelypacked structure with small voids inside the cage owing tofavorable [π···π] stacking between the two central benzenerings. The imperfect extended packing of these propeller-shaped molecules, on the other hand, generated extrinsicone-dimensional channels along the crystallographic a-axiswhich accounted for 10% of the structure volume (Figure4).31
Figure 4 Imine cage 15 prepared by Cooper and co-workers (left) and its crystal structures (right) (element colors: N—blue, C—gray, H—white)
In an [8+12] cycloimination of tris(4-formylphe-nyl)amine with chiral diamines (R,R)-1,2-cyclohexanedi-amine and (R,R)-1,2-cyclohex-4-enediamine, two distortedcube-like assemblies were obtained. These highly porousstructures were found to collapse upon desolvation.32
By functionalizing imine-based cages with long alkylchains, Cooper and co-workers produced materials withsignificantly lowered melting points that allowed access toboth liquid and glassy phases. However, the liquids werefound not to be porous as long alkyl chains appended to onecage could easily penetrate cavities of neighboring cages.33
Very recently, an alternative strategy proved successful inproducing liquids with permanent porosity: the dissolutionof imine-based molecular cages in 15-crown-5—a solventwhose molecules are too large to enter the pores.34
Mastalerz produced a tetrahedral salicylimine-basedcage 18 through the condensation of triaminotriptycene 16with salicyldialdehyde 17 (Scheme 2).35 Subsequent crystal-lization and porosity measurements revealed a high BETsurface area of 1375 m2·g–1 and exceptional selectivity foradsorption of CO2 relative to CH4.36
In a following full paper, the same group reported thepreparation of a series of peripherally substituted deriva-tives of 18, wherein the original tert-butyl group (on 17)was replaced with groups of varying steric bulk. It wasfound that in the amorphous state, most of the preparedsubstituted cages had similar surface areas of around ~700m2·g–1; however, upon crystallization, some almost doubledtheir surface areas, while others halved it. This behaviorwas interpreted to be due to dominant contributions of thecages’ internal surface to the porosity in the amorphousstate; in the crystalline state, orientation of space-sweepinglarge bulky groups had to be accounted for, and—as some ofthem could not pack closely together—it led to an increasein the accessible surface area.37
These imine-based molecular cages were shown to besolution processable. Their deposition onto a quartz crystalmicrobalance using an electrospray procedure resulted in a
Scheme 2 Synthesis of a highly porous imine-based cage 18 by con-densation of triamine 16 and dialdehyde 17 (in the crystal structure of 18, hydrogen atoms have been removed for clarity; element colors: O—red, N—blue, C—gray)
porous coating that could uptake and release vapors of aro-matic solvents.38 This approach was additionally used togravimetrically sense γ-hydroxybutyric acid (GHB) and itslactone.39
Using two triptycene-based precursors—triamine 16and tricarboxaldehyde 19—the same group discovered theself-assembly of molecular cube 20 (Scheme 3).40 In thisstrategy, each of the triptycene building blocks acted as acorner of the cube, with convergent positioning of three re-active functionalities. The two precursors alternate as cor-ners of the final cubic assembly. Mastalerz’s work on po-rous imine-based cages has been highlighted in this jour-nal.41
Scheme 3 Synthesis of a molecular cube by condensation of two trip-tycene-based fragments (for simplicity, the cube is shown schematical-ly, with each precursor color retained in the structure of the final compound)
Zhang and co-workers also reported a synthesis ofimine-based cages through a [2+3] cycloimination. Whilethese cages had low BET surface areas, they showed highselectivity for adsorption of CO2 relative to N2.42
Porous Cages Based on Boronate EstersThe dehydration of boronic acids and diols into boro-
nate esters was the first reaction to be used in the synthesisof COFs.43 Mastalerz and co-workers adapted the reversiblechemistry of boronate ester based COFs to give discrete mo-lecular capsules.44 Using triptycene-derived tetraol 21—which positioned its two catechol moieties in a convergentfashion at a 120° angle—and tris-boronic acid 22, Mastalerzand co-workers prepared molecular cage 23 (Scheme 4),whose crystal structure revealed a large void in the center.The surface area of this material was found to be 3758 m2·g–1,the highest thus far reported for porous molecular crystals.
Surprisingly, with a minimally modified derivative of21, in which the two ethyl groups are moved to the bridge-head positions of triptycene and replaced with hexyl sub-stituents, a different outcome of condensation was ob-served in the solid state.45 Instead of discrete cages being
formed, two of them quadruply interlocked to create cate-nated structure 25 (Scheme 5). The authors postulated thatthe interlocked structure allowed greater close contact be-tween alkyl groups; as expected, its porosity is quite a bitlower than that of 23: 1540 m2·g–1.
Scheme 4 Synthesis of highly porous boronate ester cage 23 from 20 molecular components (element colors: O—red, C—gray, B—yellow, H—white
4 Extrinsically Porous Molecular Crystals
In 2012, Mastalerz and Oppel reported the synthesis oftris-benzimidazolone 27 (Scheme 6) from hexaammoniumtriptycene hexachloride 26.46 Compound 27 was chosen asa candidate for the assembly of extrinsically porous crystalsbecause of the well-known propensity of benzimidazolonesto form ribbon-like hydrogen-bonded structures in the sol-id state. The trigonally symmetric orientation of the three
16(4 equiv)
19(4 equiv)
NH2
H2N
H2N
HO HO
HO
O
O
O
20
Scheme 5 Synthesis of highly porous boronate ester catenane 25 from 20 molecular components (in the crystal structure of the catenane, hy-drogens have been removed and one of the two cages is colored in blue for clarity; element colors: O—red, C—gray, B—yellow)
such moieties in 27 was expected to result in a porousstructure.
Scheme 6 Synthesis of tris-benzimidazolone 27
Indeed, 27 was found to crystallize as a highly porousstructure with a BET surface area of 2796 m2·g–1—currentlya world record for extrinsically porous molecular crystals(Figure 5, left).46 Two distinct kinds of pores are apparent inthe structure of 27: large pores roughly circular in shapeand smaller rectangular pores. This material was also foundto adsorb high amounts of CO2 (15.9 wt%) and much small-er amounts of nonpolar CH4 (1.5 wt%). The porous structureof 27 is held together by infinite tapes of hydrogen bondsestablished between the N–H and C=O groups of the ben-zimidazolone moieties of 27 (Figure 5, right).
Mastalerz and co-workers have more recently disclosedanother class of trigonally shaped molecules 28 that orga-nize into porous structures through [π···π] stacking of theirextended aromatic surfaces (Figure 6).47 Depending on theR substituents, their surface areas ranged between 206 and754 m2·g–1. These molecules were also found to be fluores-cent, boding well for potential applications in sensing.
The plot thickened when it came to the analysis of ex-tended solid-state structures of these compounds. Becauseof the weak interactions between the molecules, most ofthem are amorphous solids. However, crystallization of pe-ripherally triptycene-substituted compound 28e revealedno fewer than four polymorphs, with void volumes ranging
from 63 to 72%. Interestingly, all of these polymorphs wereobtained under identical crystallization conditions (con-centration of mesitylene solution), suggesting again the ab-sence of highly preferential interactions among the buildingblocks.48
Figure 6 Trigonal precursors to [π···π]-stacked fluorescent porous ma-terials prepared by Mastalerz and co-workers
McKeown and co-workers also reported triptycene-based organic molecules of intrinsic microporosity (OMIM),with BET surface areas in the range 515–702 m2·g–1; thesematerials were amorphous.49
In 2011, Chen’s group at the University of Texas in SanAntonio disclosed the synthesis and characterization of 29(Figure 7, top), which was elaborated in three steps fromtetraphenylmethane.50 This tetrahedral compound is orna-mented with four terminal 2,4-diamino-1,3,5-triazin-6-yl
26 27NH2
H2N NH2
H2N
H2NNH2
N
NN
N
NN
O
O
H
H
H
H
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H
H
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O
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KOAc, DMF, r.t.
71%⋅6HCl
Figure 5 Crystal structure of tris-benzimidazolone 27, highlighting the one-dimensional pores (left) and a segment of the [C=O···H–N] hydrogen-bonding tapes (right), which stabilize the structure (element colors: O—red, N—blue, C—gray, H—white; hydrogen bonds are highlighted in yellow)
N
N
N
N
R
R
N N
RR
N N
N
N
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R
28a: R = H28b: R = Me28c: R = OMe28d: R = Cl28e: R =
(DAT) groups, which were previously shown by Wuest51 toact as reliable tectons for multiple strong hydrogen bonds(Figure 7, bottom).
Indeed, upon crystallization a porous network was ob-tained (SABET = 359 m2·g–1). This hydrogen-bonded organicframework (HOF) was dubbed HOF-1 and it demonstratedhigh selectivity for acetylene in its challenging separationfrom ethene.50 Subsequently, the same group disclosed thesynthesis and characterization of DAT-terminated tetrahe-dral compound 30 (Figure 7, top), which crystallized as asixfold interpenetrated HOF, dubbed HOF-4. This extendedframework has proven to be a superior adsorbent for theseparation of ethene from ethane.52
Figure 7 Structures of precursors 29 and 30 to hydrogen-bonded or-ganic frameworks HOF-1 and HOF-4 (not shown here), respectively (top) and the hydrogen bonding motif established by the DAT moieties (bottom) (element colors: N—blue, C—gray, H—white; hydrogen bonds are highlighted in yellow)
The same hydrogen-bonding motif of DAT was com-bined with the chiral scaffold of 1,1′-bi-2-naphthol (BINOL)to produce a precursor to a homochiral and microporousHOF, dubbed HOF-2.53 The BET surface area of this frame-work was a rather moderate 238 m2·g–1, but its chiral po-rous nature allowed its use in the separation of enantio-mers of secondary alcohols. In general, higher enantiomericexcesses of the R-enantiomers were observed for alcoholswith aromatic groups (92% ee for 1-phenylethanol) relativeto their aliphatic counterparts (ee’s ranging from <4% for 2-heptanol to 77% for 2-butanol).
Expanding into planar DAT-terminated building blocks,such as trigonal compound 31 (Figure 8), Chen and co-workers constructed a framework named HOF-3, a rod-packing HOF with a moderate BET surface area of 165 m2·g–
1 and a twofold preference for binding acetylene relative toCO2.54 This selectivity, while moderate, is still highly unusu-al given that the two gases have similar geometries, dimen-sions, and boiling points.
Figure 8 Compound 31, a planar structure that organizes into rod-packing HOF-3 (not shown here)
Very recently, the same group reported HOF-5,55 aframework which is both porous (SABET = 1101 m2·g–1) andflexible, and has the highest CO2 uptake of all the HOFs re-ported by Chen’s group. This material was found to havetwo-step nitrogen adsorption, suggesting a rather flexiblestructure. Using a quadruply DAT-terminated metallopor-phyrin, another porous network—dubbed HOF-7—was re-cently constructed.56
5 Fluorinated Porous Molecular Crystals
Our adventures in the arena of porous molecular crys-tals began by accident. Initially, we were seeking to prepareMOFs starting from fluorinated rigid organic ligands, whichwere anticipated to coordinate to metals and form robustporous three-dimensional networks. We focused on exten-sively fluorinated precursors as those promised to translateinto porous materials with unique physicochemical proper-ties, and because they were synthetically inaccessible tar-gets prior to our work.
In collaboration with our colleague Olafs Daugulis, wesynthesized a series of extensively fluorinated aromaticcarboxylic acids, tetrazoles, and pyrazoles, a selection ofwhich is presented in Figure 9 (top).57 Many of these verysuccessfully reticulated into MOFs, such as 33 that wastransformed into sodalite-like framework MOFF-5 upon re-action with Cu(II). The structure of this framework isshown in Figure 9 (bottom).58
Figure 9 A few of the extensively fluorinated precursors prepared in Daugulis’ and our laboratories (top) and segments of the structure of MOFF-5 [formulated as (Cu4Cl)3(33−3H+)8(H2O)12] (bottom), prepared by coordination of triply deprotonated 33 to copper(II) (element colors: Cu—cyan, F—lime, O—red, N—blue, C—gray, Cl—yellow)
While tetrazolate-based MOFF-5 showed interesting be-havior as an adsorbent for Freon halocarbons and fluorocar-bons, it was still somewhat labile in the presence of waterand even moist air. Our rationalization of this behavior re-volved around the lower basicity of fluorinated tetrazolatesrelative to their nonfluorinated counterparts, and accord-ingly their weaker coordination to a metal.
To attempt to circumvent this stability issue, we decidedto switch from a tetrazolate to more basic pyrazolate pre-cursors. Tris-pyrazole 34 (Figure 9) was targeted startingfrom 1,2,4,5-tetrafluorobenzene (Scheme 7). One of thetwo C–H bonds of the substrate was activated to couplewith N-protected iodopyrazole 36, giving intermediate 37.This species was then subjected to a threefold couplingwith 1,3,5-triiodobenzene to give 38. The trityl protectinggroup in 38 was switched for the thermolabile Boc group inprecursor 39.
With 39 in hand, we attempted a precedented protocolfor the in-situ removal of the Boc group and MOF forma-tion. In hot DMF, the Boc group was expected to thermol-yze, yielding compound 34 with free N–H functionalities.This moiety would then be slowly deprotonated into thepyrazolate by the in-situ-formed dimethylamine (which is
the product of the thermolysis of DMF), and the pyrazolatewould slowly coordinate to the metal. The objective of thissolvothermal synthesis—typically performed without stir-ring in a sealed vial, in an isothermal oven, to minimize vi-brations—was to induce the reagents to react slowlyenough to yield single crystals of the prepared MOF.59
Upon exposure of 39 to ZrCl4 as the metal source andthe above-described solvothermal treatment, we indeedgot single crystals. They were poorly diffracting, so my (‘my’here refers to O.Š.M.’s) student Teng-Hao Chen had to col-lect data at the Argonne National Laboratory synchrotronfacility. Upon returning from Chicago and refining the ob-tained crystallographic data, he entered my office and an-nounced, “we have just crystallized the ligand [34].” Themetal was nowhere to be found in the structure. We dis-cussed this rather disappointing outcome and he retired tohis office… only to excitedly return half an hour later andtell me, “the ligand itself is porous!”
The crystal structure showed hexagonal pores that pro-trude through the crystal (Figure 10, top).60 At every othertrigonal junction, a triplet of [N–H···N] hydrogen bonds con-nected three pyrazoles (Figure 10, bottom left), forming aninfinite two-dimensional hexagonal sheet. These sheetsstacked on top of each other through electronically favor-able [π···π] stacking between the electron-rich pyrazolesand electron-poor tetrafluorobenzenes (Figure 10, bottomright).
Scheme 7 Synthesis of a trigonal extensively fluorinated pyrazole pre-cursor to porous molecular crystals
Figure 10 Crystal structure of tris-pyrazole 34 (top) showing large pores held together by hydrogen bonding between pyrazoles (bottom left) and [π···π] stacking between pyrazoles and tetrafluorobenzenes (bottom right) (element colors: F—lime, N—blue, C—gray, H—white; hy-drogen bonds are highlighted in red; coloring in the bottom right struc-ture to illustrate stacking only)
Because the extended structure of 34 was held togetheronly by weak noncovalent bonds, we were concerned that itwould be unstable after the removal of disordered solventfrom its cavities. Fortunately, that was not the case: ther-mogravimetric and variable-temperature powder X-ray dif-fraction analyses confirmed the stability of the structure toat least 250 °C, and gas sorption studies indicated an acces-sible surface area of 1159 m2·g–1. In addition, the structurewas chemically resistant to water, as well as dilute acidsand bases. While not surprising—pyrazoles do not reactwith water and are weakly acidic and basic—this findingmeant that our framework was superior in stability toMOFs and other examples of hydrolytically labile porousmolecular crystals based on, for example, imine or boronateester linkages.
Extrinsically porous crystals of 34 were shown to ad-sorb fluorocarbons, hydrocarbons, and Freon halocarbons,with weight capacities in the range of 50–70%.60 In addi-tion, we have shown that they can capture commonly usedfluorinated inhalation anesthetics, such as sevoflurane andhalothane, with similar weight capacities.61
In a further collaborative study, we have shown that theadsorption of a guest within the pores of the above nCOF(noncovalent organic framework) leads to the contraction
of the framework along the hydrogen-bonding plane, butexpansion along the [π···π] stacking direction.62 This ‘rub-bery’ behavior—unique to porous molecular crystals—couldbe quantified by indexing powder X-ray diffraction patternsand via UV/vis spectroscopy in the solid state, and repre-sented a unique piezochromic sensing mechanism.
Currently, our work in this area is trying to determinethe generality of the supramolecular organization of deriv-atives of 34. We are examining expanded versions of 34, aswell as trying to determine the relative importance of hy-drogen bonding and [π···π] stacking in the creation of theporous structure.
6 Cyclobenzoins: Shape-Persistent and In-trinsically Porous?
In parallel with the development of fluorinated porousmolecular crystals, another graduate student in my group,Qing Ji, was developing facile syntheses of shape-persistentmacrocycles using reversible chemical reactions.63 As a partof this work, he proposed utilizing the benzoin condensa-tion of terephthalaldehyde (40) to produce macrocyclicoligomers. I initially discouraged this idea as it had been at-tempted before and was reported to yield only presumedpolymers.64 Undeterred, Qing tried it anyway and, to his de-light and my surprise, obtained tetrameric macrocycle 41 in21% yield (Scheme 8).65 We named this molecule ‘cyclo-tetrabenzoin’ to emphasize its cyclic tetrameric structureand chemical origin.
Scheme 8 Synthesis of shape-persistent cyclotetrabenzoin 41 from terephthalaldehyde (40)
The crystal structure of cyclotetrabenzoin 41 revealedthe expected shape of a molecular square (Figure 11, left).More surprisingly, the extended crystal packing diagramshowed a highly ordered square grid (Figure 11, right). Thisstructure was found to be porous—although not very po-rous—with an accessible surface area of 52 m2·g–1. However,the facile synthesis of cyclotetrabenzoin 41 and its shape-persistent structure could open up routes to other analo-gous and more porous organic molecules. For example, it iseasily conceivable that more porous analogues of 41 couldbe obtained by replacing terephthalaldehyde as the startingmaterial with longer linkers based on, for example, biphe-nyl or p-terphenyl.
Figure 11 Crystal structure of cyclotetrabenzoin 41 (left) and its crys-tal packing (right) (element colors: O—red, C—gray, H—white)
A similar reaction of isophthalaldehyde resulted in a tri-meric macrocycle dubbed cyclotribenzoin, although itscrystal structure was not porous.66
7 Conclusions
What is the next for the chemistry of porous molecularcrystals? Several immediate directions could be envisioned.The first would involve synthetic expansion of the range ofstructures that organize into porous crystal lattices, andpossibly coming up with predictive rules—similar to thoseestablished for MOFs—that would guide the creation of anisoreticular series.67 While some significant progress hasbeen made,22,29 this is perhaps more essential for the ex-trinsically porous structures, whose design still involvessignificant uncertainty about whether a given precursorwill translate into a porous structure.
Secondly, the rich chemistry of these small moleculescould be explored in a postsynthetic modification sense.This direction, pioneered for the MOF series by Cohen,68
would enable the straightforward expansion of a pool ofporous molecular crystals. In principle, this postsyntheticmodification would not necessarily have to be performedon porous molecular crystals. Their solution-processablecharacter means that the porous molecular crystals couldbe dissolved, then reacted, and reprecipitated or recrystal-lized following the completion of the functionalization re-action.
Finally, while solution processability of porous molecu-lar crystals presents a very dramatic advantage over otherclasses of porous materials, it is still largely unexploited inthe context of applications, at least in our view. It is ourhope that this situation will change rather quickly.
Acknowledgment
Research in our laboratories was supported by the University ofHouston and its Grant to Advance and Enhance Research, the NationalScience Foundation (CHE-1151292 and DMR-1507664), the WelchFoundation (E-1768), and the donors of the American Chemical Soci-ety’s Petroleum Research Fund (50390-DNI10). O. Š. M. is a CottrellScholar of the Research Corporation for Science Advancement. Dr.
Merry K. Smith is acknowledged for assistance with the preparationof figures.
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