Polycyclic π-electron systems with nonbenzenoid subunits received considerable attention recently as tools for sharpening the fundamental understanding of conjugation effects and (anti)aromaticity rules. Along with fundamental studies, they opened a new chemical space for the design of advanced organic materials for opto-electronic applications. Klaus Hafner, 4 a pioneer in the development of such systems, reported on several examples including azulenes, s-indacenes, heptalenes, 8 pentalenes 9 and some of their heterocyclic derivatives. Among these latter examples azaazulenes received some attention, while azapentalenes remained neglected until recently, when they started to be investigated in the context of organic light emitting diodes (OLEDs) development. Simple azapentalenes, like 2-azapentalene (2), have not been isolated so far owing to their electronic similarity to the unstable parent carbocycle, pentalene (1) (Figure ). However, Hafner and co-workers reported 2-azapentalene derivatives bearing electron donor groups (3) (Figure ), which led to a strong stabilization of the 8π-electron framework. As only a few reports appeared on this interesting structure, we set out to further explore the chemistry of stable azapentalene derivatives including both computational and synthetic approaches. Our goal is to highlight the properties and the reactivity through some model reactions of 3, which might inspire further studies or lead to opto-electronic applications of this scaffold. The π-electron perimeter of azapentelene derivatives is isoelectronic with the parent carbocyclic pentalene. Indeed, looking at the calculated frontier orbitals of azapentalene 2 (Figure ), the replacement of a C atom to a N heteroatom does not considerably influence the electronic system. Unlike to pentalene (1) and 2-azapentalene (2), there is a cyclopentadienyl anion-type contribution to the HOMO of 3, which influences not only its stability, but also affects the reactivity of the system. The different electron distribution in 3 contributes to a larger calculated HOMO-LUMO gap (2.46 eV) compared to pentalene (1.62 eV) and 2-azapentalene (1.77 eV) (B3LYP/6-311+G (d,p) in CH2Cl2 solvent model; for further details, see section S4 in the Supporting Information). Notably, a similar substitution strategy renders pentalene itself stable as well, which was prepared by the group of Hafner, and recently new insights were reported on this structure 17 (see also section S4.3 in the Supporting Information). The electronic differences that underlie the stability and reactivity differences within the series are also reflected in the calculated (anti)aromaticity features of the molecules. In contrast to the strong global antiaromatic character of 1 and 2, NICS-XY scan reveals that in 3 the 5-membered carbocycle is weakly aromatic and the heterocyclic 5-membered ring shows a weak antiaromatic character (Figure ). The calculated ACID plots support these findings (see section S4 in the Supporting Information). Furthermore, the harmonic oscillator model of aromaticity (HOMA) indicated a more preserved local aromaticity in the carbocyclic ring (0.837) compared to the heterocyclic ring (0.634) in 3. For the π-electron perimeter of 3 a HOMA value of 0.736 was obtained, which also supports the overall stability of the molecule (the HOMA perimeter value for pentalene is -0.346, which is attributed to its antiaromatic character). Following one of the original reports 14b for the synthesis of 3, we initially attempted to perform the reaction between 6 and 7, however, the solubility of 6 in THF at -20°C was poor and no product could be isolated in this way. Alternatively, the formation of cyanin 6 was carried out from (dichloromethylene)dimethylammonium chloride (4) and dimethylcyanamide ( ) and instead of isolation, it was reacted immediately with 7 (Figure ). By performing the sequence in CH2Cl2 at room temperature in the second step to improve the solubility of 6, compound 3 was isolated as a bench-stable red solid in a moderate, 34% yield. In the 1 H NMR spectrum (500 MHz) of 3, the chemical shifts of the Hs attached to the carbocyclic ring appeared at 6.19 and and and and.68 ppm in DMSO-d6. As a comparison, the chemical shifts of lithium cyclopentadienide 21 are 5.51 and 5.32 ppm in CD3CN and DMSO-d6, respectively. The 1 H NMR spectrum of 3 was also calculated, and among the different methods the M11L functional provided the closest fit with the measured data (Table in the Supporting Information). In the X-ray crystallographic structure of 3 considerable bond-length equalization is found in the carbocycle (Figure ) that points toward a cyclopentadienyl (aromatic) character (Figure ). The equal bond lengths around the heterocyclic N supports the presence of a charge-delocalized azacyanine unit (Figure ). The absorption spectrum of 3 was not substantially affected by the solvent used (Figure ). The spectrum displays maxima around 500 nm, 375 nm and 300 nm in each solvent. These absorptions could be assigned using time-dependent density functional theory (TD-DFT, CH2Cl2 solvent model, for further details, see section S4 in the Supporting Information) calculations as the HOMO → LUMO (f = 0.0049), the HOMO-1 → LUMO (f = 0.2491) and the HOMO-2 → LUMO (f = 0.5756) transitions. The obtained maximum at 499 nm in CH2Cl2 corresponds to an optical HOMO-LUMO gap of 2.48 eV, which agrees well with the calculated energy difference in the same solvent (2.46 eV). Azapentalene 3 can be protonated by the addition of acids such as HCl and AcOH, which results in the appearance of a band at 465 nm in the UV-vis spectrum (Figure ). Our attempt to characterize the redox properties of 3 using cyclic voltammetry (CV) was unsuccessful, as the compound quickly degraded/polymerized under the measurement conditions. The electron density distribution induced by the N(CH3)2 groups determines the reactivity of 3. Specifically, reactivity towards electrophiles is expected at the carbocyclic region, while towards nucleophiles at the heterocyclic region. Nucleophilic substitution at the heterocyclic ring to exchange the NMe2 groups have been described, 14c which we could reproduce under slightly modified conditions that facilitated purification (Scheme 1a) by reducing the amount of the amine reagent. Instead of heating compound 3 in piperidine at 110°C to obtain compound 8, using toluene as a solvent and an excess (30 equiv.) of piperidine relative to 3, compound 8 could be isolated in a moderate yield (33%). We attempted the extension of this chemistry to other amines with moderate success. Indoline, having an aniline-type nitrogen, was reactive under similar conditions leading to a mixture of di- (10) and mono-substituted (11) derivatives. Upon purification, the disubstituted derivative repeatedly decomposed, while the monoindoline derivative 11 was isolated and characterized. To optimize the synthesis of 11, the reaction was repeated with only 10 equiv. indoline that led to the isolation of 11 as a dark purple solid in 29% yield. The syntheses of compounds 8 and 11 were also carried out under microwave conditions with similar results in shorter reaction times (6 h) (see Supporting Information). Upon using morpholine or piperazine and its derivatives (1-phenylpiperazine, 1-methylpiperazine, 1-(2-hydroxyethyl)piperazine) as the amine reagent, while the products could be detected (LC-MS), their isolation was not feasible due to decomposition. By addressing the reactivity of the having aromatic character in 3 towards electrophiles, several new derivatives could be isolated, and the scope of tolerated reactions could be expanded compared to the initial work by Hafner and co-workers. The previously reported formyl azapentalene 12 14c,14d could be prepared (Scheme 1b) using a modified Vilsmeier-Haack formylation in an excellent yield (95%) as a bench-stable brownish-yellow solid, and its crystal structure could also be determined (Scheme 1g). The reaction of 3 with benzenediazonium chloride provided the novel azoazapentalene 13 in good yield (73%) (Scheme 1c) as an orange-colored product, which slowly degrades at ambient conditions but can be stored at low temperature under inert atmosphere. Halogenation of the carbocycle of 3 could be an entry to its arylated and alkynylated derivatives through cross-coupling chemistries and could facilitate its integration into extended πsystems. Interestingly, maybe due to the less widespread applications of transition metal catalyzed coupling reactions in the early 1980s, Kläs and Hafner paid little attention to the halogenation of 3. Their only attempt of bromination using Br2 led to a product mixture containing mono-, di-and tribrominated derivatives, where the structure of the dibromo derivative could not be determined. We systematically studied the selective halogenations of 3 (Scheme 1d-f). Initially, we used N-halosuccinimides (NXS) as halogenating agents. The reaction of 3 with NXS (1 equiv.) in all cases (X= Br, Cl, I) led to the formation of product mixtures, while with excess reagent, the reactions could be driven towards the trihalogenated products (Scheme 1d). In case of NBS, the tribrominated derivative 14 could be obtained in excellent yield (97%). Trichlorination was less efficient (49% yield), but the selectivity of the trisubstituted product 15 remained high while the conversion of 3 was lower. Additionally, under the basic work-up, we observed some loss of product due to decomposition. Notably, under the conditions similar to the bromination/chlorination triiodinated product (16) was not detected. When the reaction was carried out in CH2Cl2/DMF solvent mixture, in which both NIS and the diiodinated product was soluble, triiodinated derivative 16 could be obtained. Unfortunately, 16 decomposed over time. Following trihalogenations, we turned to the synthesis of monohalogenated derivatives (Scheme 1e). As 1 equiv. of NXS at rt led to product mixtures, we first adjusted the temperature to tune selectivity. The reaction of 3 with NBS (0.7 equiv.) in DMF at -35°C (lower temperature led to the precipitation of 3) provided a product mixture, similar as in the rt reaction. However, using Br2 and adjusting the reaction conditions (CH2Cl2, -78°C), the monobrominated product 17 could be isolated in high yield (88%) along with some dibrominated derivative 18 (10%). The structures of 17 and 18 could be determined crystallographycally (Scheme 1g). The likely reason of this selectivity is the precipitation of the HBr salt of 17 upon the use of Br2, which prevents further incorporation of bromine. Further monohalogenated products could be obtained using NCS and NIS under low temperature in CH2Cl2/DMF solvent mixture. Notably, the iodinated derivative 20 was isolable in excellent yield, while the chlorinated compound 19 degraded during the work-up and purification steps. The successful trihalogenation and monohalogenation processes provided the interesting perspective of the synthesis of derivatives containing different halogen atoms (Scheme 1f). The reactions, using NIS and NBS, respectively, for the transformations of 17 and 20, were successful, leading to products 21 and 22 in high yields, although we observed the degradation of 21 over time. With the halogenated derivatives in hand, we probed their reactivity in model Suzuki and Sonogashira cross coupling reactions (Scheme 2). Both the tribrominated ( ) and the monobrominated (17) scaffolds were reactive in Suzuki coupling with phenylboronic acid in the presence of Pd catalyst (Scheme 2a,b). In the former case the triphenyl azapentalene 23 was obtained as a stable material in low yield (13%). Under the applied conditions disubstituted and dehalogenated products were also detected (by LC-MS) during the reaction. Monophenyl azapentalene 24 could be detected under similar reaction conditions, however, its isolation was not feasible due to rapid decomposition of the product. The Sonogashira coupling of tribromo azapentalene 14 and monobromo azapentalene 17 with phenylacetylene were unsuccessful. The reaction of 14 with TIPS-acetylene (10 equiv.) led to stable mono-(25) and disubstituted (26) derivatives in low to moderate yields, while the triacetylene product was not detected (Scheme 2c). By decreasing the TIPS-acetylene excess (6 equiv.), compound 25 could be obtained in higher isolated yield (56%). The increased stability of the TIPS-acetylene derivatives compared to the phenylacetylene derivatives could be due to the steric shielding of the acetylene moiety by the large TIPS group that could prevent side-reactions. Scheme 1. Reactivity mapping of compound 3 (ORTEP style representations are drawn at the 50% probability level, disordered H atoms are omitted for clarity).