An Iodine‐Vapor‐Induced Cyclization in a Crystalline Molecular Flask

Abstract A vapor‐induced cyclization has been observed in the host environment of a crystalline molecular flask (CMF), within which 1,8‐bis(2‐phenylethynyl)naphthalene (bpen), a diarenynyl system primed for cyclization, was exposed to iodine vapor to yield the corresponding indeno[2,1‐α]phenalene species. The cyclization process, unique in its vapor‐induced, solvent‐free nature, was followed spectroscopically, and found to occur concurrently with the displacement of lattice solvent for molecular iodine in CMF⋅0.75 bpen⋅2.25 CHCl3⋅H2O. The cyclization occurred under mild conditions and without the need to suspend the crystals in solvent. The ability of CMFs to host purely gas‐induced reactions is further highlighted by the subsequent sequential oxidation reaction of cyclized 7‐iodo‐12‐phenylindeno[2,1‐α]phenalene (ipp) with molecular oxygen derived from air, yielding 12‐hydroxy‐7‐iodo‐2‐phenylindeno[2,1‐α]phenalen‐1(12H)‐one (hipp).

The advent of crystalline molecular flasks [1,2] (CMFs) has provided abreakthrough in the crystallographic visualization of chemical processes and species. [3,4] This stems from the ability of the flexible coordination polymer in question, which is derived from 2,4,6-tris(4-pyridyl)-1,3,5-triazine (tpt) linkers and zinc halide nodes,t os well and contract upon solvent addition and loss, [5] and undergo guest exchange in as inglecrystal-to-single-crystal manner. [6] Tw os trategies have been employed within CMF chemistry that employ either p-p interactions [7] or complementary pore-guest sizes and shapes to localize guest molecules.T he former strategy allows am odular approach to be employed by modifying the planar aromatic handle. [8] This provides an anchor for postsynthetic modification (PSM) reactions that occur in the solid state and can be monitored crystallographically. [9][10][11][12][13][14][15] In the absence of an aromatic handle,m atching of the spatial dimension of the pore cavity is also av iable strategy to observe guests using crystallographic methods.This approach has been used to probe photoswitching, [16] change conformational isomerization ratios, [17,18] observe unusual molecular interactions, [19] and identify organic species, [20,21] with the notable advantage of requiring only nanogram to microgram quantities of the analyte. [3] Arange of chemical reactions have been observed within CMFs,i ncluding the conversion of amines into imines, [9,10] Huisgen cycloadditions, [11] Diels-Alder reactions, [14] and metal-catalyzed methylation [12] and bromination. [15] All of these processes occurred upon immersing aC MF that contained am odified intercalated triphenylene moiety into solutions with appropriate chemical reactants.O nly one example of achemical reaction combining gas-phase reagents and aCMF has been reported, and involved the conversion of avinyl group into epoxidation/oxidation products with the aid of ar adical initiator. [14] This reaction, however,r equired loading of the CMF with 2,2'-azobis(isobutyronitrile) and the use of forcing conditions,whereby an emulsion of crystals was heated at 80 8 8Cf or 24 hours in air.T ot he best of our knowledge,a ttempting chemical transformations in CMFs using gas-phase reagents in the absence of solvents is unprecedented. Herein, we report an iodine-vapor-mediated cyclization of 1,8-bis(2-phenylethynyl)naphthalene (bpen) to 7-iodo-12-phenylindeno[2,1-a]phenalene (ipp;S cheme 1).
Prior to loading bpen into the CMF,t he solvated framework containing cyclohexane was first prepared by asolventexchange route from ap recursor framework that had been synthesized from methanol and nitrobenzene,asreported by Fujita and co-workers. [22] Immersing the crystals loaded with cyclohexane into ac oncentrated solution of bpen in chloroform resulted in the crystals changing their color from colorless to yellow after two days.A nalysis of the crystals by single-crystal X-ray crystallography determined ah igh bpen loading in the CMF,with elemental analysis revealing an occupancyo f0 .75 and the remainder of the pores being occupied by chloroform (see below). Theb pen guests could be observed in ac rystallographic model along with two molecules of chloroform and adisordered molecule of water ( Figure 1), giving an overall composition of [(ZnI 2 ) 3 -(tpt) 2 ]·0.75 bpen·2.25 CHCl 3 ·H 2 O( 1). Thec hloroform hydrogen atom attached to C(65) is well aligned to participate in aw eak CÀH···p hydrogen bond to an alkyne group of bpen equidistant between C(56) and C(57), with an observed distance of approximately 3.45 . This interaction, coupled with apair of p-p stacking interactions between the adjacent tpt ligand and the naphthalene ring (3.8 r ing intercentroid distance) and alkyne group (3.8 r ing-alkyne intercentroid distance) of bpen, serves to order the guests within the pores of 1.T he location of bpen guests within the CMF framework 1 is shown in Figure 2.
In the absence of bpen guests and solvent, the CMF possesses large 2D channels that propagate down the crystallographic b axis and the [101] direction. [5] Thechannels are of asufficient size to allow bpen to infuse into the crystals and contain protruding iodine atoms derived from the ZnI 2 nodes,which provide apolarizing environment. These factors are expected to promote the facile adsorption of molecular iodine from the gas phase.T ot est this postulate,c rystals of 1 were removed from their mother liquor, briefly dried in air, and placed in asmall glass vial. This small vial was transferred into al arger vial containing solid iodine crystals and sealed, creating an atmosphere of iodine vapor in air that is capable of infusing into the crystals.O ver several days the crystals changed color from yellow to black, coinciding with the uptake of molecular iodine.S ingle-crystal X-ray diffraction was performed on the black crystals after seven days,resulting in the identification of astructure containing molecular iodine and aregion of highly disordered electron density,which was identified as the likely location of the guest cyclization product ipp:i ts presence was subsequently confirmed by NMR spectroscopy (see below). As expected, the structure of the host framework is comparable with that of 1.I ti s reasonable to posit that the increase in disorder of the cyclized ipp guest in 2 relative to that of bpen in 1 may be due to the displacement of ordering solvent molecules by electronically diffuse molecular iodine.While the substantial disorder prevented the unambiguous identification of asingle location for the ipp molecule,astructural model is presented in the Supporting Information in which the partially occupied, heavily restrained ipp molecule is included to illustrate its likely location within the pore of the ordered framework. The asymmetric unit, which includes the heavily restrained ipp molecule modelled within the region of highly disordered electron density,isshown in Figure 3. It must be stressed that the ipp molecule shown in Figure 3s erves only as ag uide to the reader of its likely location, and does not constitute definitive crystallographic evidence.Amodel of the same structure excluding the ipp fragment is also presented for comparison (see the Supporting Information, Figure S3). In both structures of 2,m olecular iodine is included within the pores,again disordered over several identifiable and discrete positions.I ne ach case,t he total occupancyo fI 2 is between 1.75 and 2.1 molecules per [(ZnI 2 ) 3 (tpt) 2 ]u nit, although the

Angewandte Chemie
Communications highly disordered nature of this material means that these values should be interpreted with caution. Although the overall quality of this structure was relatively low,f urther experiments were performed to unambiguously confirm the composition of 2,w hich was determined to be [(ZnI 2 ) 3 -(tpt) 2 ]·0.75 ipp·0.25 CHCl 3 ·2 I 2 .T his result was based on ac ombination of analytical techniques to determine the nature of the guest species (see below).
Single crystals of 2 were digested in [D 7 ]DMF,a nd the resulting mixture was analyzed by 1 HNMR spectroscopy ( Figure S4). Thes pectrum contained no evidence of bpen; however, two new cyclizedspecies were identified in aratio of 1:1.6. Thes ample was subjected to column chromatography using hexane as the eluent to separate the two components. Them ajor component eluted first and was determined to be the expected cyclization product ipp by 1 HNMR spectroscopy (see below) as well as by X-ray diffraction of the recrystallized product ( Figure S3). Them inor component was only isolable in trace amounts,b ut high-resolution mass spectrometry ( Figure S5) determined the unknown molecular ion to have a m/z ratio of 509.0005. This species was matched to an oxidized product of ipp (hipp;s ee Scheme 2) that is formed by (presumably subsequent) reaction with molecular oxygen ([M + Na] = 509.0014). Thec onversion of ipp into hipp in the presence of molecular oxygen has been observed previously, [23] albeit in solution and only after several weeks. This result demonstrates the ability of the CMF to host not only the iodine-induced solvent-free quantitative cyclization of bpen, but also consecutive gas-mediated reactions in an unoptimized yield of more than 35 %, which greatly exceeds the trace amounts achieved in past reports. [23] To better quantify the initial cyclization of bpen to ipp,the iodine infusion experiment was repeated in the inert argon atmosphere of ag love box. Single crystals held in this environment were analyzed by 1 HN MR spectroscopy at intervals of 12 hours,3days,and 7days ( Figure 4). Digestion in [D 7 ]DMF was undertaken in the glove box, and 1 HNMR samples were protected from atmospheric O 2 using Schlenk NMR tubes.Pure single-crystalline ipp obtained after column chromatography was also dissolved in [D 7 ]DMF in the absence of O 2 and included as ar eference.T he results show that very little conversion (< 5%)had occurred after 12 hours despite the dramatic change in crystal color from yellow to black, suggesting that either iodine infuses into the crystal prior to mediating the cyclization, or that only the surface of the crystals has undergone reaction at this time.A fter three days,however, 85 %ofthe loaded bpen had cyclized to ipp,as determined by comparing the ratio of the residual meta-phenyl resonances of bpen at 7.26 ppm to the new aromatic resonances of ipp at 7.05 ppm and 9.17 ppm. After seven days, bpen was no longer observable spectroscopically,a nd apart from residual tpt derived from digestion of the CMF and as ignal at 8.39 ppm, which was assigned to chloroform, ipp was the dominant species observed. Interestingly,d espite rigorous exclusion of oxygen from the point of iodine introduction, trace amounts of hipp were still observed in the spectra recorded after three and seven days.T hese findings can be attributed to the uptake of small amounts of molecular oxygen by 1 during the air-drying step prior to transfer into the glove box. No evidence of hipp was observed after 12 hours,d emonstrating the necessity of the iodinemediated cyclization step prior to hipp formation and supporting the conclusion that ipp is initially formed in the iodine-gas-mediation cyclization with subsequent transformation to hipp within the molecular flask in the presence of O 2 .
Thec yclization of bpen to ipp requires as ingle iodine atom from molecular iodine and liberates ap roton. The remaining iodide likely forms gaseous hydrogen iodide,which is liberated from the CMF under inert conditions.U nder aerobic conditions,t he hydrogen iodide may react further with molecular oxygen to give molecular iodine and water.
To better evaluate the degree of solvation within the CMFs 1 and 2,t hermogravimetric analysis was employed ( Figure S6). Independent analysis of bpen prior to loading into the CMF showed that the guest is thermally stable up to 230 8 8C, after which time it loses approximately 50 %o fi ts mass up to 400 8 8C. CMF 1 loses 8.1 %bymass in two steps up to at emperature of 200 8 8C, which is consistent with the crystallographic assignment of two chloroform molecules and one water molecule (predicted:1 1.8 %). Thei odine-infused CMF 2 was found to have lost 19.9 %o fi ts mass by 230 8 8C, which is consistent with the surmised presence of two equivalents of molecular iodine within the CMF (predicted: 20.0 %). Theelemental analysis results for framework 1 were indicative of incomplete bpen loading, likely involving substitutional disorder of chloroform, with ar atio of 75 %b pen to 25 %CHCl 3 ,providing matching C, H, and Npercentages  crystals with regard to guest loading, which is ak nown phenomenon in CMF systems. [22] Elemental analysis performed on 2 was also consistent with al oading ratio of 0.75, with the remaining 0.25 assigned to residual chloroform based on 1  In conclusion, we have described gas-mediated reactions that occur quantitatively within aCMF under mild conditions and without the need to activate the framework beyond the initial loading of reagents.Furthermore,the reaction occurred without any need to suspend the CMF in asolvent, simplifying methods for reaction monitoring.Inthe absence of air,bpen was converted into the cyclization product ipp by molecular iodine after seven days,a sm onitored by 1 HN MR spectroscopy.Running the transformation in air resulted in aprocess of sequential gas-mediated reactions,f irst iodine-mediated conversion of bpen into ipp,f ollowed by oxidation of ipp to hipp.The latter oxidation step proceeded with aconversion of more than 35 %after seven days without optimization, greatly improving on past solution-based reports. [23] To the best of our knowledge,this work represents the first report of sequential gas-mediated reactions in aC MF system. These results expand the utility of CMFs from solution-phase to gasphase reaction monitoring,a nd demonstrate their potential for undertaking sequential reactions in a"crystalline one-pot flask". This will be of great interest to the field of MOF-based catalysis as well as for the development of gas-sensing devices.