Tailored Synthesis of N-Substituted peri -Xanthenoxanthene Diimide (PXXDI) and Monoimide (PXXMI) Scaffolds

: The tailored synthesis of homo (A 2 ) and hetero (AB) N-substituted peri -xanthenoxanthene diimides (PXXDIs) and peri -functionalized PXX monoimides (PXXMIs) from 3-hydroxy naphthalic anhydride is described. As A 2 -type PXXDIs could be synthesized in one step, AB-type PXXDIs and PXXMIs were prepared through a modular approach capitalizing on sequential Suzuki coupling, Imidation and Pummerer reactions with very high yields. In view of their potential applications as organic semiconductors, self-organization studies were performed through liquid deposition on surfaces, depicting the formation of islands, needles and rods.


 INTRODUCTION
O-doped polycyclic aromatic hydrocarbons are attracting significant attention as materials for optoelectronic applications. 1Among the different families, perixanthenoxanthene (PXX) 2 have firstly debuted as p-type organic semiconductors to engineer flexible OLEDs. 3The re-emergence of such interesting PXX-based chromophores recently engendered synthetic programs in our and other laboratories. 4Our group has expanded the structural diversity of PXX and developed a variant of the oxidative Pummerer O-annulation reaction to prepare perisubstituted PXXs featuring ribbon-like structures with either armchair 5 or zig-zag 6 peripheries and π-extended surfaces. 7Very recently, we prepared the first mimics of naphthalene-diimide (NDI), 8 perylene-monoimide (PMI) and -diimide (PDI) molecules, 9 in which the PXX core exposes either one (PXXMI) or two (PXXDI) alkylimide groups (Figure 1). 10 N-octyl PXXMI and PXXDI display good solubility in organic solvents, green-centered UV-vis absorption, high emissive quantum yields (Φ = 40 -70%, τ = 3 -9 ns), and HOMO and LUMO levels rigidly shifted at higher energies than those measured for PDI derivatives. 10n contrast to PDIs, both PXXMIs and PXXDIs can act as p-type semiconductors.
Current synthetic route (Figure 1) gives access to A2type N-substituted PXXDIs, 10 and it involves subsequent imidation, Suzuki C-C coupling, and O-annulation reactions (Imidation-Suzuki-Pummerer strategy, ISP) as the crucial steps. 10Nevertheless, the lack of a simple protocol providing access to any N-substituted derivatives and of a synthetic plan giving AB-type PXXDIs limits the applicability of the current pathway.It is considering these drawbacks that herein we report new high-yielding synthetic paths for preparing A2-and AB-type PXXDIs as well as PXXMIs.
As one can easily anticipate, the divergent chemical transformation limiting the scope of the current synthetic route is the imidation reaction.Thus, a decision was made to install the imidic group fairly late in the synthesis (Figure 1).In this work we envisage to relegate the imidation step at the penultimate step of the synthetic plan and use either a direct oxidative Pummerer dimerization (IP route) to obtain A2-type derivatives from 3-hydroxy naphthalene imide precursors, or a sequential Suzuki-Imidation-Pummerer synthetic strategy (SIP) to give both A2-and AB-type PXXDIs.Capitalizing on the SIP strategy, a variety of N-substituted PXXMIs could also be readily prepared, including a blue-colored, NIR-emitting N-octyl peri-π-extended PXXMI.

 RESULTS AND DISCUSSION
Inspired by the protocol of Bolloweg et al. to prepare PXX through direct oxidation of naphthol with CuO, 11 our investigations debuted with a homocoupling procedure (IP strategy, Figure 1) to afford A2-type PXXDIs from the relevant N-substituted 3-hydroxy-naphthalene imide precursor.As the model reagent, we prepared naphthalene imide 4 Oct (Scheme 1).Our studies commenced by examining the homocoupling method using CuO in refluxing PhNO2, which gave 1 Oct in 13% yield.When using CuI and PivOH in DMSO at 150 °C for 5 h in air, [5][6][7]10 we improved the yield to 20%. Simltaneously to our investigations, a related work by Kamei et al. describing the high-yielding synthesis of A2type PXXDIs following the IP strategy using CuCl in DMSO at 120 °C appeared as a patent.12 In our hands, Kamei et al. conditions gave 1 Oct in 43% isolated yield.
Anticipating a potential susceptibility of the Nsubstituent with the oxidative protocol of the IP strategy, we developed a route in which the O-annulation is performed with a binaphthol precursor with shorter times (Scheme 2).In this synthetic plan, the imidation reaction is relegated to the second to last step.Bromination 10 of 3hydroxy-1,8-naphthalic anhydride 3 with Br2 (Scheme S2) followed by alkylation with MeI in the presence of DBU in MeOH 13 gave dimethyl ester 6 in 81% yield that, coupled to its boronic-ester derivative 7 through Suzuki reaction, gave tetramethyl ester 8 in 81% yield.Subsequent saponification of 8 with KOH in iPrOH followed by addition of HCl(aq.) in AcOH gave bisanhydride 9 in 81% yield.Cleavage of the methoxy groups with HBr in AcOH 14 and condensation reaction with n-octylamine afforded binaphthol diimide 13 Oct in 92% yield.Final C-O cyclization using Cu(I) salt, PivOH in DMSO under open air conditions gave final PXXDI 1 Oct in 77% yield as previously reported. 10Notably, when the O-annulation was performed without PivOH acid, the yield decreased to 41%.Having a considerable quantity of bisnaphthalene anhydride 10 in hand, one can envisage to construct a wide series of A2-type N-substituted binaphthol diimides using the relevant amines and cyclize them into PXXDIs.Considering that the IP route would potentially yield to mixtures of N-substituted PXXDIs (the A2-, AB-and B2type derivatives), we turned our gaze to the SIP route for tailoring AB-type PXXDIs (Scheme 1).
Building on the strategy developed to prepared AB-type N-substituted NDIs, 15 we first inferred that sequential condensation reactions, involving mono anhydride intermediates, could give access to AB-type PXXDIs starting from tetramethyl ester 8 (Scheme S4).Thus, we decided to undertake the preparation of a mono anhydride derivative by acid hydrolysis of 8 using several acids such as pTosOH .H2O, HCl(aq.) and TFA in different solvents (e.g., toluene, hexane and CHCl3).Unfortunately, none of the tested reaction conditions gave the monoanhydride, and only an inseparable mixture of mono and dianhydride derivatives was obtained.Therefore, we focused on the Pdcatalyzed C-C bond formation as the hetero-coupling reaction (Scheme 2).Suzuki cross-coupling between Nfunctionalized Br-derived naphthalene imide 14 Oct10 and boronic pinacol ester 7 gave dimethyl ester-monoimide 15 Oct in 59% yield.Subsequent anhydride formation in TFA followed by the deprotection of the methoxy groups and imidation reaction with 2,4,6-trimethylaniline at 150 °C, gave AB-type N-substituted diimide 13 Oct-Mes in 63% over three steps.Final Pummerer O-annulation gave targeted AB-type PXXDI 1 Oct-Mes in 89% yield.
At last, we prepared peri-functionalized PXXMIs following the SIP route (Schemes 1, S5-S6).As anticipated for the A2-type PXXDIs, intermediate 7 can be also regarded as the crucial substrate for the synthesis of PXXMIs.In fact, Suzuki cross-coupling of boronic acid 7 with the relevant aryl bromide (i.e., naphthalene 27 or perylene 28) in the presence of [Pd(dba)2] and SPhos afforded bi-aryl compounds 18 and 22 in quantitative and 59% yield, respectively.Alkaline hydrolysis followed by acidic-catalyzed cyclization gave the anhydride intermediates in high yields.In the case of 22, subsequent imidation reaction with n-octylamine and deprotection of methoxy groups using 1-decanethiol (NaOH in NMP) gave targeted monoimide derivative 24.On the other hand, removal of the methoxy groups in anhydride 18 with BBr3 gave intermediate 20 that was transformed into the given binaphthyl imide derivative (21 Oct/Teg/Mes ) by imidation reaction using the relevant amine.O-annulation of dihydroxy intermediates 21 Oct/Teg/Mes and 24 using CuI and PivOH in DMSO at 120-150 °C yielded targeted PXXMIs 2 Oct/Teg/Mes (58%-93%) and 2 Per (65%).All intermediates and final products were unambiguously identified by 1 Hand 13 C-NMR spectroscopy and HR-MS spectrometry.
The photophysical studies of PXXDIs and PXXMIs were performed in CH2Cl2 solutions by steady-state UV/Vis absorption and emission spectroscopy (Table 1).The absorption spectra of A2-and AB-type N-substituted PXXDIs show the characteristic features of imidefunctionalized PAHs 10 with an absorption maximum  centered at 538 nm (ε = 43500 M -1 cm -1 ) and 540 nm (ε = 50600 M -1 cm -1 ) for 1 Oct and 1 Oct-Mes , respectively.As expected, the N-substitution has a small effect on the UVvis absorption properties, caused by the desymmetrization of the PXXDI and possible aggregation phenomena as described for the perylene bisimide. 17Similarly, the emission profiles and fluorescence quantum yields are negligibly influenced by the chemical nature of the Nsubstituent (Figure S54).Analogously, the PXXMIs bearing different N-substituents depict very similar absorption profiles with a maximum band at 525, 528 and 529 nm for 2 Oct , 2 Teg and 2 Mes respectively (Figures 2 and S55).Alike to PXXDIs, the luminescence spectra of both 2 Teg and 2 Mes display equivalent emission profiles with high fluorescence quantum yields (Φ ~ 70%) to that of 2 Oct (Φ = 68%).The effect of the peri-fusion of a naphthalene unit in PXXMI 2 Per causes a strong red-shift of the UV-vis absorption profile when compared to that of 2 Oct , displaying the lowest-energy transition at 628 nm (ε = 23100 M -1 cm -1 ).PXXMI 2 Per exhibits a red emission centered at 710 nm (Φ = 3% and 10% in aerated CH2Cl2 and toluene, respectively).While the solvent seems to have a negligible effect on the UV-Vis absorption, a bathochromic shift of the emission peak has been observed upon increasing the solvent polarity (Figures S56-S57).Likely, this effect can be attributed to an intramolecular charge transfer character of the lowest-energy transition (i.e., from the O-doped electron donating perylene π-scaffolding to the electrondepleting imide group).It is noteworthy to indicate that the chemical nature of N-substituents has a small effect on the redox properties of both PXXMI and PXXDI (Table 2).As depicted in the diagram, the N-substituents display very similar HOMO and LUMO energy levels, whereas only 2 Per has a significantly lowered LUMO level (Figures 3, S58 and  S59).(10).c HOMO and LUMO energies are calculated from the respective halfwave potential by assuming that the formal potential of the ferrocene redox couple, taken as a reference, is at -5.1 eV vs. vacuum and following the formulae: EHOMO = E 1/2 ox,1 -5.1 (eV) and ELUMO = E 1/2 red,1 -5.1 (eV).d Additional peaks were observed while oxidizing, suggesting that an induced aggregation or minor decomposition is probably occurring the CV cycling.e Calculated using the optical gap following the formula: ELUMO = EHOMO + optical gap (eV).nd stands for not determined.
Figure 3. Frontier orbital energies for the PXXMIs and PXXDIs in CH2Cl2.Dashed lines correspond to calculated LUMO energies using optical gap in the same solvent using the formula: ELUMO = EHOMO + optical gap (eV).The formal potential of the reference Fc/Fc + redox couple is assumed to be at -5.1 eV vs. vacuum.
As solution processability represents one of the hallmarks for preparing nanostructured materials to be used as organic semiconductors, we studied the selforganization properties of 1 Oct , 2 Oct and 2 Per by AFM imaging of the nanostructures (Figure 4, left) formed on Al2O3 surfaces upon spin-coating deposition of a CHCl3 solution (c = 0.25 mg mL -1 ).While multilayered nanometer-sized leaf-like and needle-like objects for 1 Oct and 2 Oct have been obtained, amorphous aggregates were observed for 2 Per .It is worth to underline that the morphologies constituted by 1 Oct and 2 Per are formed through a typical Volmer-Weber growth mechanism, 18 for which the growth is preferred to occur on the soft-matter rather than on the Al2O3 substrate.Solvent vapor annealing (SVA) was employed as post-deposition treatment to enhance the crystallinity of the nanostructures as well as their homogeneity. 19The spin-coated samples were thus exposed to a saturated atmosphere of CHCl3 vapors for 16 h at r.t.(Figure 4, right).For 1 Oct , SVA procedure led to a redistribution of the material to a uniform surface distribution.On the other hands, under SVA conditions PXXMIs 2 Oct and 2 Per reorganize into needles (l < 10 µm, w < 400 nm) and rods (0.25 < l < 4.5 µm, w < 200 nm), respectively.

 CONCLUSIONS
In conclusion, we have developed novel syntheses affording highly luminescent and soluble homo and hetero N-substituted PXXDIs and peri-functionalized PXXMIs.A2-type PXXDIs can be accessed following either a direct Pummerer dimerization or a sequential SIP strategy.Relegating the imidation to a final stage of the synthesis allowed us to also develop a tailored synthetic route to prepare AB-type PXXDIs.The SIP methodology could also be used to readily prepare PXXMIs featuring either different N-substituents or peri-π-extension.Noteworthily, the ability to form selectively nanostructures from solution casting and trigger their reorganization on surfaces make these molecules ideal to further program functional materials featuring optimized performances as organic semiconductors, just like their PDI and NDI analogues.

 EXPERIMENTAL SECTION
General Experimental Methods.NMR spectra ( 1 H-, 13 C-NMR) were recorded on a Bruker AVANCE III 600 MHz equipped with an Inverse QCI CryoProbe™ or Bruker AVANCE III HD 400 MHz NMR spectrometer equipped with a Broadband multinuclear (BBFO) SmartProbe™ or on a Bruker ADVANCE III HD 300 MHz NMR.Chemical shifts are reported in ppm using the solvent residual signal as an internal reference (CDCl3: H = 7.26 ppm, C = 77.16ppm; CD2Cl2: H = 5.32 ppm, C = 54.00 ppm; (CD3)2CO: H = 2.05 ppm, C = 29.84ppm, 206.26 ppm; (CD3)2SO: H = 2.50 ppm, C = 39.52 ppm).The resonance multiplicity is described as s (singlet), d (doublet), dd (doublet of doublets), t (triplet), q (quartet), quint (quintuplet), m (multiplet), and br (broad signal).Coupling constants, J, are reported in Hertz.All spectra were recorded at 25 °C unless specified otherwise.In the case of molecules 9, 10, 13 Oct the J values of defined the dd patterns are close enough that apparent triplets t, thus the two can be mistaken.In such cases we report the resonance multiplicity as dd indicating only one J value.Infrared spectra (IR) were recorded on a Shimadzu IR Affinity 1S FTIR spectrometer in ATR mode with a diamond monocrystal.Mass spectrometry: (i) High-resolution ESI mass spectra (HRMS) were performed on a Waters LCT HR TOF mass spectrometer in the positive or negative ion mode.(ii) High-resolution MALDI mass spectra (HRMS) were performed on a Waters Synapt G2-Si QTOF mass spectrometer.(iii) High resolution Atmospheric pressure chemical ionization (APCI) and Atmospheric Solids Analysis Probe (ASAP) mass spectrometry was performed on a Waters LCT Premier quadrupole time of flight mass spectrometer operating in the atmospheric pressure chemical ionization mode; all these analyses were carried out at Cardiff University.Melting points (m.p.) were measured on a Gallenkamp apparatus in open capillary and have not been corrected.UV-Vis absorption spectra were recorded on air equilibrated solutions at r.t. with an Agilent Cary 5000 UV-Vis-NIR spectrophotometer, using quartz cells with path length of 1.0 cm.Emission spectra were recorded on an Agilent Cary Eclipse fluorescence spectrofluorometer or with a PerkinElmer LS-50 spectrofluorometer, equipped with a Hamamatsu R928 photomultiplier tube.Quantum yield values in solution of compound 2 Per is calculated using Coumarin 153 in air equilibrated ethanol as a standard (Φ = 0.53) 16 and 1 Oct-Mes , 2 Mes and 2 Teg are calculated using Rhodamine 6G 16 in air equilibrated ethanol as a standard (Φ = 0.94) following the method of Demas and Crosby. 20Cyclic Voltammetry was realized using a Metrohm-Autolab PGSTAT204 potentiostat.Adsorption silica chromatography columns (SCC): Merck silica gel 60 (40-63 µm) was used.Chemicals were purchased from Sigma Aldrich, TCI, Acros, Fluorochem and Alfa Aesar and used as received, unless otherwise stated.Solvents were purchased from VWR, Sigma Aldrich and Acros, and deuterated solvents from Sigma Aldrich, Fluorochem and Cambridge Isotope Laboratories and used as received.THF and CH2Cl2 were dried on a Braun MB SPS-800 solvent purification system and further dried over activated 4 Å molecular sieves.Anhydrous conditions, when necessary, were achieved by keeping all glassware in oven at 140 °C overnight and then allowed to cool down under vacuum followed by drying the two-neck flask by flaming with heat-gun under vacuum and purging with N2.The inert atmosphere was maintained using Nitrogen-filled balloons equipped with a syringe and needle that was used to penetrate the silicon stoppers used to close the flask's necks.

5-hydroxy-6-(2-hydroxynaphthalen-1-yl)-1H,3Hbenzo[de]isochromene-1,3-dione 20.
In an oven dried single-neck round bottom flask, methoxy derivative 19 (1.00 g, 2.60 mmol) was dissolved in dry CH2Cl2 (30 mL).The solution was cooled down to 0 °C and BBr3 (1 M in CH2Cl2, 26.0 mL, 26.0 mmol) added.The resulting solution was stirred at r.t. for 30 hours.The reaction mixture was poured on crushed ice and extracted with EtOAc.The organic layers were dried over MgSO4, filtered and evaporated under reduced pressure to yield title compound 20 as a yellow solid (903 mg, quantitative  Oct .In a single-neck round bottom flask, DIPEA (144 mg, 1.11 mmol) was added to a suspension of dihydroxy-binaphthylanhydride 20 (200 mg, 0.56 mmol) and n-octylamine (108 mg, 0.84 mmol) in 1,4-dioxane (75 mL).The reaction mixture was stirred under reflux for 20 hours.After cooling down to r.t., the solvent was evaporated under reduced pressure and the solid residue suspended in HCl(aq) (10 % w/w) and extracted with CHCl3.The combined organic layers were dried over MgSO4, filtered and evaporated under reduced pressure.The crude was purified by silica gel chromatography (eluents: hexane:EtOAc 5:2) to give title compound 21 Oct as a yellow solid (256 mg, 97%).M.p.: 166 -167 °C. 1     (10 mL).The reaction mixture was stirred under reflux for 20 hours.After cooling down to r.t., the solvent was evaporated under reduced pressure and the solid residue suspended in HCl(aq) (10 % w/w) and extracted with CHCl3.The combined organic layers were dried over MgSO4, filtered and evaporated under reduced pressure.The crude was purified by silica gel chromatography (eluent: EtOAc) to give title compound 21 Oct Mes .In a single-neck round bottom flask, imidazole (344 mg, 5.301 mmol) was added to a mixture of dihydroxybinaphthyl-anhydride 20 (150 mg, 0.42 mmol) and 2,4,6trimethylaniline (68.0 mg, 0.50 mmol).The reaction mixture was stirred at 130 °C for 3 hours under N2.After cooling down to r.t., HCl(aq) (10 % w/w) was added and the resulting solution was extracted with CH2Cl2.The combined organic layers were washed with H2O, dried over Na2SO4, filtered and evaporated under reduced pressure.The crude was purified by silica gel chromatography (eluents: CH2Cl2:MeOH 100:0 to 99:1) to give title compound 21 Mes

Supporting Information
Synthesis schemes, 1 H and 13 C NMR spectra of isolated compounds, photophysical characterization data, and AFM images (PDF).
The Supporting Information is available free of charge on the ACS Publications website.

Figure 4 .
Figure 4. AFM height imaging of 1 Oct (a, b), 2 Oct (c, d) and 2 Per (e, f) on Al2O3 before (left) and after 16 h of SVA (right) using CHCl3 at r.t.Deposition achieved through spincoating of a 0.25 mg/mL CHCl3 solution of the relevant molecule on Al2O3.