Synthesis and Properties of NitroHPHAC: The First Example of Substitution Reaction on HPHAC

Abstract

Hexapyrrolohexaazacoronene (HPHAC) is one of the N-containing polycyclic aromatic hydrocarbons in which six pyrroles are fused circularly around a benzene. Despite the recent development of HPHAC analogues, there is no report on direct introduction of functional groups into the HPHAC skeleton. This work reports the first example of nitration reaction of decaethylHPHAC. The structures of nitrodecaethylHPHAC including neutral and two oxidized species (radical cation and dication), intramolecular charge transfer (ICT) character, and global aromaticity of the dication are discussed.

1. Introduction

Introduction of functional groups into π-conjugated systems is a straightforward way to tune their chemical and physical properties. A nitro group is one of the most useful groups for such purpose. Aromatic nitro compounds have been studied and utilized for medicines, pesticides, dyes, pigments, plastics raw materials, and so on. The functional group strongly stabilizes electron-rich polycyclic aromatic hydrocarbons (PAHs) and can be transformed to many other functional groups by simple reactions [1]. When the nitro group is introduced to large π-conjugated compounds, the LUMO levels would be sufficiently lowered so that nucleophiles could directly attack the π-conjugated systems. The nitro group can be easily transformed into an amino group, which is recognized as one of the most powerful electron-donating groups, as well. Therefore, nitration reaction is one of the first choices for further derivatization of aromatic compounds. Recently, large π-conjugated materials with a nitro group and their derivatives have attracted continuing attention from many research areas [2,3,4,5,6,7,8,9,10,11,12,13,14].

Hexapyrrolohexaazacoronene (HPHAC) is a nitrogen-embedded PAH, consisting of circularly connected pyrroles around a benzene core and is easily prepared from hexapyrrolylbenzene by the Scholl oxidation using FeCl₃ [15], 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in the presence of trifluoromethanesulfonic acid [16], or N-bromosuccinimide (NBS) [17]. The HPHAC π-system consists of local π-systems of six pyrroles and one benzene and has a non-aromatic character in the whole molecule. Due to the pyrrole moieties, on the other hand, multiple oxidation levels of HPHAC are reversibly generated, and its dication shows global aromaticity owing to the cyclic conjugation of a 22π-electron system. So far, HPHAC-hexabenzocoronene-hybridized [18], ethylene-bridged [19], periphery-expanded [20,21], core-expanded [16], azulene-fused [22], β,β-thieno-fused [23], chiral [24], antiaromatic [25], and σ-dimerized [26] types of its analogues have been reported. However, a peripheral substitution reaction of HPHAC has never been reported yet. Functionalization of HPHACs has all been dependent on the composed pyrroles employed. Herein, we report the first example of nitration on decaethylHPHAC (DEHPHAC 1a), leading to nitroDEHPHAC 2a (Scheme 1). The fundamental properties of nitroDEHPHAC 2a were investigated by NMR and absorption spectroscopy, single crystal X-ray structure analysis, and theoretical calculations.

2. Results and Discussion

DEHPHAC 1a was synthesized from N-(2,3,4,5,6-pentafluorophenyl)-1H-pyrrole via decaethylated hexapyrrolylbenzene DEHPB by S_NAr and successive Scholl reactions in accordance with the previously reported procedure [15,27]. The nitration of 1a was then carried out with silver nitrite. In contrast to the cases of corrole and porphyrin [28,29], DEHPHAC 1a did not dimerize by this oxidant but was transformed into nitroDEHPHAC 2a in a 51% yield (Scheme 1). The nitration mechanism is not unclear at this moment although we suppose a coupling of cation radical 2a^•+ with nitrogen dioxide (•NO₂) plays a key role. The crude product was purified by silica-gel column chromatography with hexane and toluene as the eluent. The structure of 2a was unambiguously identified by ¹H-NMR, high-resolution LDI-TOF MS, and X-ray single-crystal structure analyses.

The ¹H-NMR spectrum of 2a exhibited signals due to one β-proton of pyrrole and fifty protons of ethyl groups, and these signals appeared in the lower fields compared to those of 1a due to an electron-withdrawing effect of the nitro group. Single crystals were fortunately obtained by vapor diffusion of methanol into the toluene solution of 2a. The X-ray crystal structure analysis revealed the averaged bond length of the N-O moiety is 1.233(6) Å, the value of which is similar to that of nitrobenzene (1.226 Å) [30]. The molecules in the crystal adopted a slipped columnar structure with π–π stacking distances of 3.406 and 3.449 Å, calculated by the mean planes of 24 atoms forming hexaazacoronene. The values are almost the same as the sum of van der Waals (vdW) radii of carbon atoms (ca. 3.4 Å) (Figure 1A,B).

To investigate the intramolecular charge transfer (ICT) character between the electron-rich HPHAC moiety and the nitro group, the absorption spectra of 1a and 2a were considered by the comparison with density functional theory (DFT) and the time-dependent density functional theory (TD-DFT) calculations of decamethylHPHACs (DMHPHACs 1b and 2b), where all ethyl groups of 1a and 2a were replaced by methyl groups for simplicity (Supplementary Information Sections 7, 8, 9, and 10). The cut-off of 2a in a CH₂Cl₂ solution is bathochromically shifted by ca. 200 nm compared to that of 1a (Figure 2). A characteristic broad band around 540–740 nm is ascribed to the mixed transitions of HOMO–LUMO and HOMO−1–LUMO, according to TD-DFT calculations (Supplementary Information Section 7). Figure 3 shows the molecular orbitals (MOs) of 1b and 2b. By the introduction of a nitro group on DMHPHAC 1b, both HOMO and LUMO levels are lowered, and the decrease of the LUMO energy is larger than that of HOMO (△E = 0.86 for LUMO and 0.39 eV for HOMO). The LUMO is derived from the nitro group, mainly located at the nitro group, and slightly developed to the DMHPHAC skeleton. The LUMO+1 of 2b is correlated to the LUMO of 1b, and the LUMO+2 and LUMO+3 of 2b are from degenerated LUMO+1 and LUMO+2 of 1b. As a result, the HOMO–LUMO gap of nitroDMHPHAC 2b is narrower than that of 1b, which is attributable to the broad absorption band in the longest wavelength region of the ICT transition. In fact, positive solvatochromism was observed for 2a in various solvents (Supplementary Information Section 4) because of strong stabilization of polarized LUMO of 2a by polar solvents. NitroDEHPHAC 2a showed little emission.

Electrochemical properties of 2a were examined by cyclic and differential pulse voltammograms (CV and DPV) (Figure 4). CV of 2a showed two reversible oxidation waves at −0.20 and 0.07 V against a ferrocene/ferrocenium ion couple, values of which are low compared to those of 1a. Thus, oxidative titration of 2a was performed with pentachloroantimony(V) as monitoring the absorption spectra and resulted in the two-step changes with isosbestic points from neutral to radical cationic and then to dicationic species (Figure 5 and Supplementary Information Section 7). The peak maxima of radical cationic and dicationic species appeared in the visible to NIR region at 627 and 688 nm together with a broad band centered at ca. 1150 nm and at 784 and 884 nm with a broad band centered at ca. 1450 nm, respectively, which are characteristic for the previously reported the HPHAC radical cations and dications [15].

For better understanding of the structures and electronic properties of oxidized species, the radical cation and dication of 2a were aimed to be prepared by controlling the amount of an oxidant employed (Scheme 1). Both species were quantitatively obtained by the oxidation of proper amounts of silver(I) hexafluorophosphate as the oxidant, successfully isolated as hexafluorophosphate salts (isolated yields were not determined) and stable enough to handle under air in the solid states. Single crystals of 2a^•+[PF₆⁻] were obtained by slow vapor diffusion of hexane into the chlorobenzene solution and were subject to X-ray analysis. The crystal turned out to be composed of one molecule of 2a^•+[PF₆⁻] and one and a half molecules of chlorobenzene in the asymmetric unit, and the radical cation molecule of 2a^•+ was revealed to form a π-dimeric structure by an inversion center in the unit cell (Figure 6 and Supplementary Information Section 5). The closest atoms between the neighboring molecules in the π-dimer faced by the convex side are found in the benzene core, and the distance is 3.173 Å. The distance of the mean planes of 24 hexaazacoronene atoms was 3.348 Å. These values are shorter than the sum of vdW radii of carbon atoms, strongly suggesting the π-dimer formation between two radical cations [31,32,33,34].

The X-ray crystal structure of dication 2a²⁺[PF₆⁻]₂ was also determined and illustrated in Supplementary Information Section 5. In general, the bond-length alternation (BLA) is important to discuss the nature of π-system.

Table 1. Selected bond lengths of 2a, 2a^•+[PF₆⁻], and 2a²⁺[PF₆⁻]₂ (the bonds in nitro-substituted pyrrole moiety were omitted due to the disorder) [Å] ¹.

Bond	Neutral	Radical Cation	Dication
Cα-Cα Cβ-Cβ Cα-Cβ	1.482(3) 1.435(3) 1.391(5)	1.463(8) 1.418(4) 1.407(7)	1.442(6) 1.396(5) 1.429(5)
Cα-N	1.394(4)	1.392(6)	1.389(7)

¹ Averaged values are shown with standard deviations calculated by the following Equation:

shows the selected bond lengths of the pyrrole rings of neutral 2a, radical cation 2a^•+, and dication 2a²⁺. By increasing the number of oxidation states, the averaged bonds of C_α-C_α and C_β-C_β become shorter, and the bond of C_α-C_β becomes longer, while that of C_α-N is nearly identical. These results indicate the delocalized radical and cation as observed for the previous system [15,16]. ¹H-NMR of 2a²⁺ clearly exhibits a downfield shift for the β-proton of pyrrole moiety (δ = 3.53 ppm) compared with that of neutral 2a (Supplementary Information Section 6), demonstrating global aromaticity of 2a2⁺ as observed for 1a2⁺. The anisotropy of the induced current density (ACID) calculation for 2b2⁺ also supports global aromaticity (Supplementary Information Section 8). Notably, although the chemical shifts of β-protons of 2a2⁺ and 1a2⁺ are almost the same, ethyl protons of 2a²⁺ appear to be upfield-shifted (CH₂: Δδ ≈ 0.15 ppm) despite the existence of the electron-withdrawing nitro group. Based on the nucleus-independent chemical shift (NICS) calculation, global aromaticity of 2a²⁺ seems to be weaker than 1a²⁺ (Supplementary Information Section 8). Therefore, the slight upfield shifts of ethyl protons of 2a²⁺ would reflect the weaker global aromaticity, and the similar chemical shift values of β-proton of 2a²⁺ and 1a²⁺ observed would be due to cancellation of the conflicting effects of downfield (NO₂) and upfield (diminished global aromaticity).

{∑(x_i−<x>)²/(n−1)}^1/2

(1)

3. Conclusions

The first example of nitration reaction of DEHPHAC 1a giving nitroDEHPHAC 2a was presented. The ICT character of 2a from the electron-rich HPHAC core to the periferal nitro group was confirmed by diagnosis of the solvatochromiclly-shifting absorption centered at ca. 640 nm with TD-DFT calculations. Similar to the DEHPHAC 1a, nitroDEHPHAC 2a also showed stable redox properties. Crystallographic analysis of 2a in not only neutral but radical cationic and dicationic states was performed to reveal a slipped columnar structure for the neutral molecule, π-dimeric structure for the radical cation, and anion-separated structure for the dication. These properties can be applied for supramolecular chemistry and organic electronics such as field effect transistor. Studies including the further derivatization and functionalization of HPHACs are currently underway in our laboratory.

4. Materials and Methods

¹H and ¹³C-NMR spectra were recorded on JEOL (Akishima city, Japan) AL-400 at 400 MHz or Bruker Biospin (Osaka, Japan) AVANCE III at 500 MHz for ¹H and 100 MHz for ¹³C with use of tetramethylsilane (0 ppm) or residual solvent for ¹H (7.26 ppm for CDCl₃) and ¹³C (77.01 ppm for CDCl₃) signals, and if not otherwise noted, all spectra were measured in CDCl₃ at 298 K. Cyclic voltammetry (CV) measurements were performed on a CH Instruments-ALS612B electrochemical analyzer using a standard three-electrode cell consisting of Pt working electrodes, a Pt wire counter electrode, and an Ag/AgNO₃ reference electrode under a nitrogen atmosphere. The potentials were calibrated with ferrocene as an external standard. IR measurements were performed with Thermo Fischer Scientific (Tokyo, Japan) Nicolet iS5 FT-IR. Decomposition points were determined with Büchi M–565 and not corrected. Electronic spectra were recorded on a JASCO (Hachioji, Japan) V–570 UV–VIS/NIR spectrophotometer. High-resolution laser desorption/ionization time-of-flight mass spectra (HR LDI-TOF) were measured on JEOL (Akishima, Japan) JMS-S3000.

All reactions were carried out under nitrogen atmosphere. Thin-layer chromatography (TLC) analyses were carried out using silica gel 60 F₂₅₄ and aluminum oxide 60 F₂₅₄, neutral (Merck Millipore, Tokyo, Japan). Silica-gel chromatography was performed on Silica Gel 60 N (spherical, neutral) purchased from Kanto Chemical Co., Inc. (Tokyo, Japan) Alumina column chromatography was performed on activated alumina (about 200 mesh) purchased from FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan). Dry solvents were purchased from Kanto Chemical Co., Inc. (dichloromethane).

4.1. Synthesis of N-[2,3,4,5,6-Pentakis(3, 4-Dimethylpyrrolyl)Phenyl]Pyrrole (DEHPB)

Sodium hydride dispersion in paraffin oil (ca. 60%, 380 mg) was weighed in a round flask, and the oil was removed by dry hexane. After drying, sodium hydride was weighed to be 207 mg (8.63 mmol), and the flask was sealed by a rubber septum. N-(2,3,4,5,6-Pentafluorophenyl)-1H-pyrrole [15] (180 mg, 0.773 mmol) in dry DMF (10 mL) was added to the flask by a syringe at 0 °C, then 3,4-diethylpyrrole (577 mg, 4.68 mmol) in dry DMF (5.0 mL) was added dropwise at the same temperature, the mixture was stirred, and then, the temperature was raised to 40 °C. After being stirred for 20 h, the reaction mixture was poured into water. The mixture was extracted with ethyl acetate. The organic extract was washed with water, dried over Na₂SO₄, and concentrated under a reduced pressure to give a crude product as a white solid. The crude product was purified by trituration with MeOH to give DEHPB as a white powder (468 mg, 0.624 mmol; 81%): ¹H-NMR (400 MHz) δ 0.93 (m, 30H), 2.21 (q, J = 7.4 Hz, 20H), 5.70 (s, 4H), 5.72 (s, 6H), 6.00 (m, 2H), 6.16 (m, 2H); ¹³C-NMR (100 MHz) δ 14.80, 14.82, 14.84, 14.90, 14.93, 14.99, 18.49, 18.51, 110.08, 117.34, 117.45, 121.35, 126.39, 126.57, 126.58, 126.61, 132.13, 133.03, 133.41, 133.86. DI MS m/z 749 (M⁺+1). IR (ATR) ν_max = 1494, 1488, 1122, 773, 723 cm⁻¹ (Supplementary Information Sections 1–3).

4.2. Synthesis of 1,2,3,4,5,6,7,8,9,10-Decaethylhexapyrrolo [2 ,1,5-bc:2′,1′,5′-ef:2′′,1′′,5′′-hi:2′′′,1′′′,5′′′-kl:2′′′′,1′′′′,5′′′′-no:2′′′′′,1′′′′′,5′′′′′-qr][2a,4a,6a,8a,10a,12a]Hexaazacoronene (DEHPHAC 1a)

To a CH₂Cl₂ (100 mL) solution of DEHPB (369 mg, 0.492 mmol) was added a CH₃NO₂ (5 mL) solution of FeCl₃ (2.8 g, 18 mmol) at room temperature. After being stirred for 3 h at 60 °C, the mixture was cooled to 0 °C, and then, hydrazine hydrate (5 mL) was added. The mixture was further stirred for 5 min at 0 °C. The mixture was extracted with toluene. The organic phase was washed with water, dried over Na₂SO₄, and concentrated under a reduced pressure. The residue was dissolved in a small amount of toluene and then passed through a short column of alumina. The eluate was concentrated to give a reddish brown solid. The solid was recrystallized from toluene/MeOH to give 1a as orange crystals (250 mg, 0.359 mmol, 67%): ¹H-NMR (400 MHz, C₆D₆) δ 0.85 (m, 30H), 2.09 (q, J = 7.4 Hz, 20H), 5.66 (s, 2H); ¹³C-NMR (100 MHz) δ 15.33, 16.98, 17.18, 17.87, 17.99, 18.05, 104.95 (2 kinds of C), 105.63, 106.25, 106.30, 106.60, 117.61, 117.98, 118.48, 118.77, 120.20, 122.01, 122.56, 122.72, 122.75, 122.99. HR-LDI-TOF MS: calcd. for C₅₀H₅₂N₆⁺: 736.4253; found: 736.4287. IR (ATR) ν_max = 1630, 1448, 1371, 1360, 744 cm⁻¹ (SI Sections 1–3).

4.3. Synthesis of nitroDEHPHAC 2a

Dichloromethane (50 mL) was added to a mixture of DEHPHAC 1a (49 mg, 0.067 mmol) and AgNO₂ (100 mg, 0.65 mmol). The suspension was stirred vigorously at 20 °C for 1.5 h. After addition of hydrazine hydrate (ca. 1 mL), the solution was concentrated under a reduced pressure. A minimum solution of the residual solid in toluene was put on a silica-gel column filled with hexane, and then, the column was eluted with toluene. Green fractions were combined and then concentrated in vacuo to give 2a (27 mg, 0.034 mmol, 51%) as a dark green solid: ¹H-NMR (400 MHz) δ 6.47 (s, 1H), 2.37–2.78 (m, 20H), 1.11–1.27 (q, 27H), 1.05 (t, 3H, ³J = 7.3 Hz). ¹³C-NMR (125 MHz) δ 133.75, 131.91, 126.19, 125.62, 125.00, 124.43, 124.10, 123.92, 123.79, 123.67, 122.87, 121.61, 120.73, 119.77, 119.35, 118.79, 108.25, 107.84, 106.60, 106.44, 106.29, 103.60, 102.02, 19.171, 18.14, 17.99, 17.657, 16.980, 16.87, 16.47, 15.31, 15.02. (The signals due to core benzene carbons were not found). HR-LDI-TOF MS: calcd. for C₅₀H₅₁N₇O₂⁺: 782.4104; found: 782.4106. IR (ATR) ν_max = 1626, 1360, 1309, 1275, 1240 cm⁻¹ (SI Sections 1–3).