# Radical-Formation Management: Towards Aza-Analogues of the Benzothioxanthene Imide

Darío Puchán Sánchez, Pierre Josse, Monika Mutovska, Benjamin Siegler, Magali Allain, Korentin Morice, Philippe Blanchard, Frédéric Gohier, Tangui Le Bahers, Cyrille Monnereau, et al.

► To cite this version:

Darío Puchán Sánchez, Pierre Josse, Monika Mutovska, Benjamin Siegler, Magali Allain, et al. Radical-Formation Management: Towards Aza-Analogues of the Benzothioxanthene Imide. ChemistryEurope, 2023, 2 (1), pp.6264-6285. 10.1002/ceur.202300071. hal-04500800

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# Radical-Formation Management: Towards Aza-Analogues of the Benzothioxanthene Imide

Darío Puchán Sánchez,[a] Pierre Josse,[a] Monika G. Mutovska,[b] Benjamin Siegler,[a] Magali Allain,[a] Korentin Morice,[a] Philippe Blanchard,[a] Frédéric Gohier,[a] Tangui Le Bahers,[c] Cyrille Monnereau,[c] Yulian Zagranyarski,[*b] Dominik Lungerich,[*d, e] and Clément Cabanetos*[a, f]

While benzothioxanthene imide (BTI) has shown promise in organic electronics and more recently in photodynamic therapy, its full potential remains yet undiscovered. In this context, this study repots the synthesis and characterization of aza derivatives in which the characteristic sulfur atom is replaced by an amino group. Adapted from the synthetic route of the BTI, a way was found to control the electronic structure of the radical

intermediates, by means of a simple chemical modification. As a result, either the thermodynamically six-membered or the kinetically favored five-membered ring regioisomers can selectively be accessed. Photophysical rationalization of their structure-property relationships confirmed the richness, versatility and tunability of this class of rylene imide-based dyes.

## Introduction

Rylene imide dyes play, due to their charge transport properties, synthetic accessibility and remarkable photo/thermal stabilities, a key role in various modern and emerging applications.[1] Along with these demonstrations, significant efforts were devoted to the functionalization of such polycyclic aromatic hydrocarbons (PAHs).[2] Hence, owing to the creativity of organic chemists, myriads of synthetic strategies were reported resulting in new design principles and original structures. Amongst them, the benzothioxanthene imide (BTI, Figure 1) recently caught our attention, resulting in notable achievements: firstly, the targeted modification of different positions within its π-conjugated core,[3] and secondly, the application of this dye as an active component in organic solar cells (OSCs),[3a,4] light emitting diodes (OLEDs),[5] field effect

transistors (OFETs),[6] and even for photodynamic therapy (PDT).[7]

• Previous work

<figure><img src="image_4.png" /><figcaption>BTI</figcaption></figure>

• This work

<figure><img src="image_5.png" /><figcaption>BAI</figcaption></figure>

VS

<figure><img src="image_6.png" /><figcaption>BCI</figcaption></figure>

<caption>Figure 1. Structure of the BTI and the two aza based regioisomers reported herein (BAI and BCI).</caption>

[a] D. P. Sánchez, Dr. P. Josse, B. Siegler, Dr. M. Allain, K. Morice, Dr. P. Blanchard, Prof. F. Gohier, Prof. Dr. C. Cabanetos
Univ Angers, CNRS, MOLTECH-ANJOU, SFR MATRIX
49000 Angers (France)
E-mail: clement.cabanetos@cnrs.fr

[b] Dr. M. G. Mutovska, Prof. Y. Zagranyarski
Faculty of Chemistry and Pharmacy
University of Sofia
1 James Bourchier blvd., 1164 Sofia (Bulgaria)
E-mail: zagranyarskiyulian@gmail.com

[c] Prof. T. Le Bahers, Prof. C. Monnereau
ENS de Lyon, CNRS, Université Claude Bernard Lyon 1
Laboratoire de Chimie UMR 5182
69342 Lyon (France)

[d] Prof. D. Lungerich
Center for Nanomedicine
Institute for Basic Science (IBS)
IBS Hall, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722 (South Korea)
E-mail: d.lungerich@yonsei.ac.kr

[e] Prof. D. Lungerich
Department of Nano Biomedical Engineering (NanoBME)
Advanced Science Institute
Yonsei University
50 Yonsei-ro, Seodaemun-gu, Seoul, 03722 (South Korea)

[f] Prof. Dr. C. Cabanetos
Building Blocks for Future Electronics Laboratory (2BFUEL)
IRL CNRS 2002
Yonsei University
Seodaemun-gu, Seoul, 03722 (South Korea)

[g] Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ceur.202300071

[h] © 2023 The Authors. ChemistryEurope published by Chemistry Europe and Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
<figure><img src="image_7.png" /></figure>

Continuing our efforts to further explore the reactivity and structure-properties relationships, we initiated a study aiming at preparing aza analogues of the **BTI** in which the sulfur-constituting atom is replaced by a nitrogen to *i*) fine-tune its optoelectronic properties and *ii*) provide extra functionalization possibilities.[8] Hence, using the synthetic route adapted from the **BTI**, which involves the Pschorr reaction,[3e] we found out that a subtle chemical modification on the amine precursor critically impacts the selectivity of the intramolecular radical cyclization, resulting in the preferential formation of either a six or five-membered nitrogen-containing ring; i.e., the target **BTI** analogue (**BAI** for benzoacridino imide) or the carbazole-based regioisomer (**BCI** for benzocarbazole imide), respectively (Figure 1). Synthetic routes, structure elucidations, proposed mechanisms and comparison of their (significantly different) optoelectronic properties are thus discussed and reported herein.

## Results and Discussion

Adapted from the recently optimized synthesis of the **BTI**, the key intermediate **2** was prepared by reacting **1** with 2-nitroaniline under Buchwald-Hartwig conditions before reducing its aromatic nitro group into an amine to afford compound **3** (Scheme 1).

<figure><img src="image_8.png" /><figcaption>Scheme 1. First anticipated synthetic route to **BAI-H**.</figcaption></figure>

<figure><img src="image_9.png" /><figcaption>**Figure 2.** Computed electron spin densities of both radical species (di and mono).</figcaption></figure>

Isolated in good yields, the latter was subsequently engaged in a Pschorr-like reaction, i.e., in presence of amyl nitrite. Interestingly, this reaction led to the formation of a major compound (4) that turned out to be different from the predicted one (**BAI-H**). Characterization by nuclear magnetic resonance spectroscopy (NMR) indeed revealed the presence of 9 diastereotopic aromatic protons while only 8 were expected (Figure S5) and mass spectrometry a molecular weight of 385.1668 g·mol⁻¹ vs 356.1525 g·mol⁻¹ (for the expected **BAI-H**). Based on reports from the literature,[9] these results converged toward the formation of triazole 4 that was later confirmed by X-ray diffraction on single crystals grown by slow evaporation method (Table S1). Non-emissive when directly out of the column, we noticed that solutions used for NMR characterization started to spontaneously produce a gradual blueish fluorescence upon exposure to light. Resulting from the formation of a new product (Figure S25), the full and quantitative conversion was reached by irradiating a fresh solution of 4 in toluene at 254 nm (150 W). Known as the Graeb-Ullmann reaction,[10] triazole can indeed undergo a type-II ring cleavage upon photolysis to form a diradical intermediate by nitrogen extrusion.[11] Based on this scenario, 4 can indeed evolve into the diradical 5 that, in turn, lead to the formation of five-membered nitrogen-containing ring (**BCI-H**) by intramolecular cyclization of 6, followed by the rearomatization of the resulting intermediate 7 (Scheme 2).

In agreement with the possible resonance forms of the diradical, generated by the photolysis of the triazole, the presence of spin density at the appropriate position to afford the isolated five-membered nitrogen-containing ring **BCI-H** (which structure was confirmed by X-ray analysis) was supported by density functional theory (DFT) calculations at the M06-2X/def2-TZVP/def2-SV(P) level of theory. As shown in Figure 2 (Table S6–S7), the diradical exhibits a distinct spin

<figure><img src="image_10.png" /><figcaption>Scheme 2. Structure of the isolated compound **BCI-H** resulting from the photolysis of 4 and possible mechanistic pathway and further N-methylation to **BCI-Me**.</figcaption></figure>
<figure><img src="image_11.png" /></figure>

density on the naphthyl moiety favoring a five-membered ring formation and thus leading to the kinetically favored **BCI** product. Hence, to avoid the formation of the triazole during the Pschorr-like reaction, the secondary amine of **2** was protected to a tertiary one to give methylated derivative **8** (Scheme 3).

After reduction of **8** to amine **9**, the protected intermediate **(9)** was then naturally subjected to a source of nitrite, resulting in the specific formation of the desired **BAI-Me**. Since the monoradical (**10**) can potentially also lead to the formation of the **BCI-Me** regioisomer with a spin density mainly localized on the aryl moiety (Figure 2), DFT calculations nonetheless revealed **BAI-Me** to be thermodynamically favored by 6.9 kJ/mol, thus making **BCI-Me** the kinetic product. Hence, through the generation of either a di- or monoradical species (Graebellmann vs Pschorr), by means of a *N*-alkylation protection, it is thus possible to control the selectivity of the intramolecular cyclization and therefore afford specifically either the kinetic (**BCI-Me**) or thermodynamic (**BAI-Me**) regiosomers.

Beyond this synthetic peculiarity, both isomers exhibit significantly different optoelectronic properties, as confirmed by UV-vis absorption and fluorescence measurements (Figure 3-A and Table 1). In order to afford a more reliable comparison with the **BAI-Me**, the carbazole based **BCI-H** was methylated to afford its regioisomer entitled **BCI-Me** (Scheme 2). All measurements were routinely performed in chloroform, a solvent of intermediate polarity, and well suited for singlet oxygen generation measurements (*vide infra*). Hence, regarding the absorption spectra, **BCI-Me** was characterized by a band centered in the violet part of the visible spectrum, with a maximum absorption wavelength ($\lambda_{max}$) at 409 nm. In comparison, that of the **BAI-Me** appears significantly shifted towards lower energies (504 nm), even beyond that of the **BTI** (455 nm). The molar extinction coefficient of **BCI-Me** was also significantly reduced compared to its six-membered regioisomer, which value was, on the other hand, close to that of **BTI**. Moreover, other noticeable differences were highlighted from these spectra. First, **BCI-Me** was found to be devoid of vibronic structure, suggesting an intramolecular charge transfer (ICT)

A)

<figure><img src="image_12.png" /></figure>

B)

<figure><img src="image_13.png" /><figcaption>**Figure 3.** A) Absorption (solid) and emission (dashed line) spectra of **BTI** (black), **BAI-Me** (red) and **BCI-Me** (blue). B) energetic diagram determined from PYSA and UV-visible spectroscopy.</figcaption></figure>

character of the transition and extensive reorganization processes between the ground and excited state. By contrast, and despite a much-lowered transition energy, **BAI-Me** displays a very marked vibronic structure with a dominant 0–0 vibronic transition, strongly reminiscent of the typical signature found in perylene diimide. This characteristic also contrasts with the benchmark **BTI** compound, that shows a slight vibronic shoulder, suggesting an intermediate character of the transition, between **BCI-Me** and **BAI-Me**. This is indeed confirmed by TD-DFT calculations with computed $D_{CT}$ index, quantifying the charge transfer character of a transition,[12] of 2.9 Å, 1.6 Å and 1.1 Å for **BCI-Me**, **BTI** and **BAI-Me** respectively. The differences observed in the absorption spectra also translate to the emission properties of the molecules. While **BCI-Me** indeed shows a structureless emission centered at 460 nm with a relatively large Stokes shift (ca. 2700 cm⁻¹, confirming the ICT features of the transition), **BAI-Me** presents a moderate Stokes shift (ca. 450 cm⁻¹) and an envelope, still characterized by a dominant 0–0 vibronic transition, that almost perfectly mirrors its absorption spectrum. Comparison with the benchmark **BTI** highlights that the latter appears to be a combination of the features recorded on both nitrogen-based compounds with a large Stokes shift (ca. 2350 cm⁻¹) and a marked vibronic progression, characteristic of **BCI-Me** and **BAI-Me** respectively. On the other hand, while

<figure><img src="image_14.png" /><figcaption>**Scheme 3.** Synthetic route to **BAI-Me**.</figcaption></figure>
<figure><img src="image_15.png" /><figcaption>**Table 1.** Optical data recorded on BTI, BAI-Me and BCI-Me.</figcaption></figure>

<table><thead><tr><th>Compound</th><th>λ<sub>abs</sub> max<br>[nm]</th><th>ε<br>[M<sup>-1</sup> cm<sup>-1</sup>]</th><th>λ<sub>em</sub> max<br>[nm]</th><th>Φ<sub>f</sub><sup>[a]</sup><br>solution</th><th>Φ<sub>Δ</sub><sup>[b]</sup></th><th>λ<sub>film onset</sub><br>[nm]</th><th>Φ<sub>f</sub><sup>[a]</sup><br>powder/coated film</th><th>E<sub>g</sub><sup>opt</sup><br>[eV]</th><th>HOMO<sup>[c]</sup><br>[eV]</th><th>LUMO<sup>[d]</sup><br>[eV]</th></tr></thead><tbody><tr><td>BTI</td><td>455</td><td>24000</td><td>510</td><td>0.99</td><td>0.01</td><td>538</td><td>0.09/0.07</td><td>2.30</td><td>-5.98</td><td>-3.68</td></tr><tr><td>BAI-Me</td><td>504</td><td>29100</td><td>516</td><td>0.99</td><td>0.01</td><td>582</td><td>0.04/0.015</td><td>2.13</td><td>-5.76</td><td>-3.63</td></tr><tr><td>BCI-Me</td><td>409</td><td>12700</td><td>460</td><td>0.85</td><td>0.15</td><td>464</td><td>0.09/0.04</td><td>2.67</td><td>-5.96</td><td>-3.29</td></tr></tbody></table>

[a] Φf = Fluorescence quantum yield, measured using Coumarin-153 as reference (Φf = 0.45 in MeOH). [b] ΦΔ = Singlet oxygen quantum yield measured using Phenalenone as reference (Φf = 0.95 in CH₂Cl₂). [c] Measurement by photoemission yield spectroscopy in air (PYSA). [d] LUMO = HOMO-E₉ₐᵢopt.

BTI and BAI-Me show similar luminescence quantum yields, close to unity, it was found to be slightly reduced for BCI-Me (qf = 0.85). The latter compound was nonetheless demonstrated to sensitize singlet oxygen (φΔ = 0.15; Figure S26), thus highlighting the contribution of an intersystem crossing (ISC) pathway in the excited state deactivation. Although TD-DFT predicts similar and relatively weak spin orbit coupling values for both BAI-Me and BCI-Me (Figure S30), it is worth underlying that the associated oscillator strength for the lowest transition (which similarly affect both the absorbance and radiative kinetic constant for spontaneous emission) appears significantly decreased in BCI-Me, in agreement with experimental data (ε = 29100 cm⁻¹ vs 12700 cm⁻¹). This feature may explain the reduction of fluorescence efficiency in favor of intersystem-crossing pathway. In solid state, all three compounds undergo aggregation caused quenching (Figure S27) with Φf of ca 0.09 measured for both BTI and BCI-Me and 0.04 for the red-shifted BAI-Me, on their powder form. Note that this effect was even more saliant on coated films from concentrated solutions (Table 1). In parallel, thin films were also used to determine and compare their frontier orbital energy levels by combining UV-visible and photoemission yield spectroscopy (PYSA) measurements (Figure S28 and S29) on thin films. Hence, from the diagram plotted in Figure 3-B, it was found that replacing the constituting sulfur atom (BTI) by an amino group (BAI-Me), mainly results in the destabilization of the highest occupied molecular orbital (HOMO) level. Interestingly, an antagonist effect was highlighted in the case of the BCI-Me since only the lowest unoccupied molecular orbital (LUMO) was found to be significantly affected by the cyclization into the carbazole ring (BTI vs BCI-Me).

## Conclusions

To sum up, the synthetic route to BTI was successfully adapted and transposed to the preparation of its aza analogue (BAI). Characterization of the latter revealed that replacing the sulfur by an amino group is an attractive strategy to fine tune the electronics while preserving impressive emitting properties. Moreover, it is noteworthy that the acridine constituting nitrogen atom brings an extra and orthogonal reactive site for grafting and/or solubility purposes. Apart from this practical and applicative aspect, rationalization of the mechanisms involved in the reaction also highlighted the key role of this functionalization/protection (conversion of this secondary amine into a tertiary one) to afford

the target compound. If not performed before the Pschorr-like reaction, the expected intramolecular radical cyclization spontaneously evolves toward the selective formation of a triazole that, in turns, undergoes a photoassisted Graebe-Ullmann reaction yielding the kinetic carbazole-based regioisomer (BCI). Investigation of their energetics revealed that controlling the position, size and nature of the heteroatom-containing ring (5 vs 6 membered ring), appears to be an appealing and straightforward strategy to independently fine tune the frontier orbitals (HOMO or LUMO), the absorption profiles and emission properties (photosensitizer and/or fluorophore) of these dyes. The replacement of the sulfur atom by a nitrogen in the characteristic six-membered heteroatom containing ring (BTI vs BAI) was indeed found to reduce the band gap through the destabilization of the HOMO level, while the formation of the carbazole, a contrario, results in an increase of the LUMO level and therefore, a broader gap. Moreover, though still highly fluorescent, the carbazole derivative (BCI) was demonstrated to promote singlet-to-triplet Inter-System Crossing since a non negligible singlet oxygen photosensitization quantum yield was measured. Consequently, as a more general and final statement, this work confirms the richness, versatility and tunability of these synthetically accessible and yet overlooked class of dyes from both a chemical and photophysical perspectives.

## Supporting Information

The authors have cited additional references within the Supporting Information.[13]

## Acknowledgements

D. P. S. and K. M. acknowledge the MITI of the CNRS and the ANR (BTXI-Apogee, ANR-20-CE05-0029) respectively for funding their PhDs program. The research was supported by the Institute for Basic Science (IBS-R026-Y1).

## Conflict of Interests

The authors declare no conflict of interest.
<figure><img src="image_16.png" /></figure>

Data Availability Statement

The data that support the findings of this study are available in the supplementary material of this article.

Keywords: benzothioxanthene imide · dye chemistry · organic chemistry · radical reactions · structure-property relationship

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Version of record online: November 27, 2023