Dehydrogenative C–H Phenochalcogenazination

Abstract

Heavy-atom-modified chalcogen-fused triarylamine organic materials are becoming increasingly important in the photochemical sciences. In this context, the general and direct dehydrogenative C–H phenochalcogenazination of phenols with the heavier chalcogens selenium and tellurium is herein described. The latter dehydrogenative C–N bond-forming processes operate under simple reaction conditions with highly sustainable O₂ serving as the terminal oxidant.

“I shall not decide whether that smell belongs to both, or whether tellurium is often associated with the new substance. Nevertheless, as a reminder of the affinity of the latter with tellurium, I have named it selenium.”¹ Upon the discovery of the latter element in 1818, Berzelius had already noted the chemical similarity of newly found selenium with already known sulfur and tellurium. He also noted some important redox differences. Another essential difference within the chalcogen group lies with the variation of covalent radius, which approximatively doubles from oxygen to tellurium.²

Vast numbers of organic heterocyclic structures are known with oxygen and sulfur, yet considerably fewer with selenium and almost none with metalloid tellurium. However, the chemistry of selenium and tellurium is becoming increasingly important in the field of heterocyclic chemistry, associated to the emergence of novel properties.² The latter are becoming a research priority in the field of bioactive compounds³ and, in particular, organic materials and catalysts (Figure 1).⁴⁻⁸

Figure 1.

Recent selected Se- and Te-containing heterocyclic materials and catalysts.

Meanwhile, the cross-dehydrogenative phenothiazination reaction has grown into a straightforward synthetic tool for the direct access to important triarylamine structures (Scheme 1).⁹ Its most important conceptual feature is that it represents a rare case of intermolecular dehydrogenative amination reaction, wherein no catalyst nor additive is required, apart from a mild oxidant.¹⁰ Importantly, even trivial O₂ can serve as an efficient oxidant in this reaction, conferring on it a highly sustainable character.¹¹ Its specificity is moreover excellent, in particular for phenothiazines as N–H substrates (PSZH, X = S) and phenols and related electron-rich arenes as C–H substrates.⁹ Until now, however, this reaction has been mostly limited to phenothiazines as the N–H coupling partners. The reason for this high specificity is well-understood: PSZHs combine a low N–H bond dissociation energy (BDE)¹² and low oxidation potential with N-centered radical persistency.¹³ These features facilitate their oxidative interception with phenols or/and phenol radicals into a C–N bond-forming cross-dehydrogenative coupling process. But how exactly limited are the PSZHs backbones as coupling partners? Can the bridging chalcogen atom X be varied? Some authors have already noted in earlier works that phenoxazine POZH (X = O) is also a competent N–H substrate in the dehydrogenative C–H chalcogenazination reaction.⁹ This finding, along with the rising interest for heavy-atom-modified chalcogen-fused triarylamine organic materials (Figure 1),³⁻⁸ encouraged us to investigate the larger chalcogens. Thus, the aim of the present work is to explore whether or not phenoselenazines (PSeZHs, X = Se) and phenotellurazines (PTeZHs, X = Te) can also act as efficient N–H substrates.

Scheme 1. Dehydrogenative Phenothiazination Reaction.

After investigating several synthetic routes from the literature, we selected a simple 2,2′-diododiarylamine pathway under basic conditions with elemental selenium or tellurium to furnish the desired PXZH azines in high yields.⁷ This approach is inexpensive, easy, mild, versatile in terms of functional group tolerance, and importantly, scalable. The synthetic results are summarized in Scheme 2 (see also the Supporting Information (SI)). Generally, the yields are excellent for the selenium analogues and encouraging for the tellurium ones, which is presumably due to the larger and more-strained heterocyclic structure of the latter. Typical functional groups such as chloro, methoxy, methyl, and CF₃ were otherwise well-tolerated.

Scheme 2. PXZH Synthesis, Isolated Yields.

These new PSeZHs and PTeZHs were then evaluated as N–H coupling partners in the O₂-mediated cross-dehydrogenative phenochalcogenazination of some characteristic phenols. For this, we utilized a basic aerobic method recently developed for phenothiazines (PSZH).⁷ To our satisfaction, the method afforded high yields with almost identical conditions than required for PSZHs and POZH (X = S and O, respectively), moreover with excellent functional group tolerance (Scheme 3; see also the SI). Indeed, electron-donating (methyl, methoxy) and electron-withdrawing groups (chloro, bromo, CF₃) were well-accommodated. Even a tyrosine derivative¹⁴ could be obtained (PSeZ_23), albeit in low yield. The method is moreover easily scalable. For instance, PSeZ_12 was obtained in 84% yield on a 2 mmol scale.

Scheme 3. Dehydrogenative C–H Phenochalcogenazination with Selenium and Tellurium: Isolated Yields.

Two mmol scale.

K₂HPO₄ was utilized instead of K₂CO₃.

150 °C, 18 h.

We were then able to obtain an X-ray structure of one of these heavy-chalcogen-fused triarylamine structures, that of PSeZ_7 (Figure 2, Scheme 4). Very similar to that observed in the known cases of oxygen and sulfur, the PSeZ moiety sits mostly perpendicular to the plane of the phenol moiety. Surprisingly, however, the potential and characteristic intramolecular OH···N hydrogen bond does not seem to take place within this crystal. Indeed, the pyramidal-shaped triarylamine moiety is pointing in the opposite direction, with respect to the OH group, which itself is pointing toward a solvent molecule.

Figure 2.

X-ray structure of PSeZ_7, 50% probability level, side and front view. Compound PSeZ_7 crystallized with one diisopropyl ether molecule. The solvent molecule has been omitted for clarity (see the SI).

Scheme 4. Characteristic Differences from X = O to Te.

Characteristic ¹H NMR signals in DMSO-d₆. X-ray structure of POZ_7 and PSZ_7: see ref (13). X-ray structure of most resembling PTeZH: see ref (15).

Other characteristic features are the expected longer C–X bonds (from 1.3865(15) Å for X = O to 1.8971(16) Å for X = Se), and the considerably shorter C–X–C angles, from 117.24(10)° for X = O (quasi-regular and flat hexagonal heterocycle) to 94.61(7)° for X = Se (heavily distorted heterocyclic ring). While no X-ray structure of a tellurium congener could be obtained at this stage, the heterocyclic distortion therein is expected to be even greater, with a C–Te–C angle expected at ca. 91°, and a C–Te distance expected at ca. 2.1 Å.¹⁵

Based on literature precedents with X = S,¹³ the dehydrogenative C–H phenochalcogenazination reaction is expected to run along a radical mechanism, as depicted in Scheme 5. The phenochalcogenazine PXZH undergoes hydrogen atom abstraction (HAT) upon reaction with O₂ under basic conditions to generate a persistent PXZ^• mostly nitrogen centered neutral radical. The latter key species can accumulate, eventually triggering HAT from the phenol. The phenol radical generated in this manner is then intercepted by PXZ^• to form the cross-dehydrogenative C–N coupling product. In support of this mechanism, a recently published study demonstrated that all phenochalcogenazines (X = O, S, Se, Te) have a similarly low oxidation potential (determined by cyclic voltammetry), associated with a mostly N-centered neutral radical persistency (determined by EPR spectroscopy after O₂ exposure).⁷ Although some small differences were observed in the case of the larger PTeZH congener, which seems, according to its EPR profile, to accommodate a mostly protonated radical cation intermediate PTeZH^• +, these altered features do not seem to forbid the C–N cross-dehydrogenative coupling reactivity, as illustrated in Scheme 3.

Scheme 5. Proposed Mechanism.

In summary, we demonstrated that the dehydrogenative C–H phenochalcogenazination reaction is a general concept, which can be extended to include selenium and tellurium. The latter afford the corresponding heavy-atom chalcogen-fused triarylamine materials in good yields, while utilizing only O₂ as a most sustainable terminal oxidant. This new synthetic tool should facilitate the development of heavy-atom-based fused organic materials.

Supporting Information Available

CCDC 2063310 contains the supplementary crystallographic data for this paper (compound PSeZ_7). These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: + 44 1223 336033. The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.1c00573.

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The authors declare no competing financial interest.