RSC Advances PAPER View Article Online View Journal | View Issue The Suzuki–Miyaura reaction as a tool for modification of phenoxyl-nitroxyl radicals of the Cite this: RSC Adv.,2018,8,26099 4H-imidazole N-oxide series† Yury A. Ten, a Oleg G. Salnikov,b Svetlana A. Amitina, a Dmitri V. Stass,bc Tatyana V. Rybalova, ab Maxim S. Kazantsev, ab Artem S. Bogomyakov, d Evgeny A. Mostovich ab and Dmitrii G. Mazhukin *ab 2-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-(4-iodophenyl)-4,4-dimethyl-4H-imidazole 3-oxide reacts with phenylboronic acid and its substituted derivatives in a cross-coupling reaction of the Suzuki–Miyaura type to form 5-biphenyl derivatives of 4H-imidazole-N-oxide. Interaction of the same compound with B2(pin)2 in the presence of PdCl2(PPh3)2 proceeds through the formation of intermediate 1,3,2- dioxoborolane and leads to the product of homocoupling: biphenyl-bis(imidazole). Oxidation of the resultant imidazoles with lead dioxide quantitatively yields stable conjugated phenoxyl-nitroxyl mono- Received 13th June 2018 Creative Commons Attribution-NonCommercial 3.0 Unported Licence. and diradicals, which are of interest as electroactive paramagnetic materials. The crystal structure of the Accepted 13th July 2018 monoradical, 2,6-di-tert-butyl-4-[1-oxido-4-(biphenyl-4-yl)-5,5-dimethyl-1H-imidazole-2(5H)-ylidene] DOI: 10.1039/c8ra05103h cyclohex-2,5-dienone, its magnetic susceptibility, EPR spectra of the obtained hybrid radicals in solution, rsc.li/rsc-advances and cyclic voltammetry characteristics of 4H-imidazoles were studied. Introduction oxide series (Chart 1),9 we turned our attention to the possibility of modifying the para-haloaryl group at the 5th position of the The cross-coupling reaction of the Suzuki–Miyaura type1 can be heterocycle using Pd-catalyzed cross-coupling reactions, in This article is licensed under a undoubtedly considered as one of the fundamental methods for particular, the Suzuki–Miyaura process. constructing aromatic and heteroaromatic ensembles in the On the one hand, the introduction of an electron- synthesis of biologically active compounds for pharmaceutical withdrawing type of substituent possessing an ÀM-effect into 2 Open Access Article. Published on 20 July 2018. Downloaded 10/1/2021 11:45:19 PM. chemistry as well as in the chemistry of new materials (prep- the para-position of the 5-aryl moiety should lead to the addi- aration of components of optoelectronic devices3 and liquid- tional stabilization of the radical center owing to further crystalline semiconducting oligomers4) and in organic photo- distribution of the electron density of an unpaired electron over voltaics.5 Recent research on the Suzuki–Miyaura reaction the conjugated system. On the other hand, further functional- includes extensive studies of various substrates involved in this ization of hybrid radicals means developing their practical process (for example, low-reactive aryl chlorides, aryl uorides, or tosylates),6 a wide range of reagents (boronic acids and their derivatives),7 and several generations of palladium catalysts with different ligand environments.8 Continuing the research on the reactivity of new stable radicals, i.e., hybrid phenoxyl-nitroxides of the 4H-imidazole N- aNN Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 9 Acad. Lavrentyeva Ave., Novosibirsk, 630090, Russia, [email protected] bNovosibirsk State University, 2 Pirogova Str., Novosibirsk, 630090, Russia cVoevodsky Institute of Chemical Kinetics and Combustion SB RAS, 3 Institutskaya Str., Novosibirsk, 630090, Russia dInternational Tomography Center SB RAS, 3A Institutskaya Str., Novosibirsk, 630090, Russia † Electronic supplementary information (ESI) available: Synthetic procedures, analytical and spectroscopic data for all new compounds. Experimental and simulated ESR spectra for the new radicals, CV data for 4H-imidazole N-oxides. Chart 1 Examples of stable hybrid radicals: 4H-imidazole N-oxide CCDC 1564701. For ESI and crystallographic data in CIF or other electronic based phenoxyl-nitroxides (PN); 1,2,3-dithiazolo-1,2,4-thiadiazinyls format see DOI: 10.1039/c8ra05103h (DTA-TDA). This journal is © The Royal Society of Chemistry 2018 RSC Adv.,2018,8, 26099–26107 | 26099 View Article Online RSC Advances Paper applicability because of creation of new promising dyadic and radical with a mild selective reagent whose redox potential triadic molecular systems. cannot change the paramagnetic status of the substrate. In this While developing fundamentally new smart devices based respect, a study on Pd-catalyzed C–C cross-coupling reactions on fully organic materials, researchers have become more (particularly, the Suzuki–Miyaura process) involving various interested in the design and construction of dyads and triads of types of persistent radicals was carried out here under the DA (donor–acceptor) or ADA (acceptor–donor–acceptor) types, conditions of both methods. where the group containing a stable radical moiety plays the For example, thermally unstable nitroxyl radicals stabilized role of the acceptor.10 These systems can be considered molec- by nitroxyl group conjugation with the benzene nucleus (t- ular switches (transforming from a neutral state to a zwitter- butylaryl, tetrahydroquinolinyl, [3,1]-benzoxazinyl, and dihy- ionic or diradical form in solution under the inuence of droacridinyl type) were introduced into the Suzuki–Miyaura external stimuli, i.e., temperature, pressure, or light), and some reaction in the form of their stable precursors, namely, of them can have properties of conductors in a solid form.11 secondary amines. Aer formation of the cross-coupling prod- Typical examples of such dyads and triads are shown in Chart 2. ucts, the latter were transformed into target nitroxides with m- As for stable hybrid radicals, only a few representatives of CPBA in a yield of 37–70%.13 At the same time, more robust this type of paramagnetics were synthesized by scientists in the iodoarene derivatives of the benzotriazinyl radical (Blatter's last decade. For instance, resonance-stabilized planar 1,2,3- radical),14a–c verdazyl radical,14d and iso-indolinoxyls14e readily dithiazolo-1,2,4-thiadiazinyl12a (Chart 1) and related radicals12b reacted in cross-coupling with either arylboronic acids or aryl- possess highly delocalized and easily tuned spin distributions. triolborate salts, which in contrast to parent acids possess Therefore, the wide range of physical and chemical properties greater reactivity. Depending on the number of iodoarene of thiazyl-based radicals make them useful building blocks for groups in these radicals, mono-, bis-, and tris-cross-coupling magnetic and conductive materials as well as coordinating products were obtained without losing a radical center. The ligands. yields ranged from 97% for the mono-cross-coupling product to Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Depending on the kinetic stability of radical types, there are 67% for bis- and 52% for the tris-phenyl-substituted compound. two fundamentally different methods for their functionaliza- As to the cyclic nitroxide based on an imidazole nucleus, to the tion. The rst method represents the interaction of their best of our knowledge, there is only one report about the diamagnetic precursors directly along a reactive group with Suzuki–Miyaura reaction involving nitronyl nitroxyl radicals various nucleophilic or electrophilic reagents, and the radical containing an ortho(meta)-iodophenyl group at the C-2 atom of center is generated at the nal stage, when the product is the heterocycle. The authors explained a rather low yield of treated with an oxidizing agent (or an excess of an electrophilic cross-coupling products in this reaction (40–43% for the ortho- reagent). The second method consists of treating the stable iodophenyl derivative and 44% for the meta-iodophenyl deriv- ative) by competitive destruction of a nitronyl nitroxide occur- This article is licensed under a ring at the elevated temperature under typical conditions of the Suzuki process (80 C, 2 h).15 Accordingly, it was interesting to nd out how hybrid Open Access Article. Published on 20 July 2018. Downloaded 10/1/2021 11:45:19 PM. phenoxyl-nitroxide radicals would behave under the conditions of the Suzuki–Miyaura reaction and whether they would be sufficiently stable to retain the paramagnetic center. Besides, Pd-catalyzed cross-coupling reactions involving 5-(haloaryl)-4H- imidazole derivatives and their N-oxides are not mentioned in any databases. Results and discussion To conduct cross-coupling experiments, the para-iodoarene substituted derivative of 4H-imidazole N-oxide was chosen as a model substrate because solely iodo derivatives show the greatest reactivity among other haloaryl compounds and produce quantitative yields of biphenyls under the classical Suzuki reaction conditions. A diamagnetic precursor of the hybrid radical, key 5-(p- iodophenyl)substituted 4H-imidazole 3-oxide 1, was synthe- sized in 6 stages based on Friedel–Cras acylation of an iodo- benzene excess with iso-butyric acid chloride followed by bromination of 4-iodo-iso-butyrophenone 2, treatment of Chart 2 Some electroactive and photoactive dyads and triads based bromo compound 3 with hydroxylamine, and hydrolysis of the on stable radicals: oxophenalyloxyl (A),10i phenoxyl-imidazolyl (B),10d,f formed 2-hydroxylamine oxime 4 by boiling with concentrated di-tert-butyl-ortho-semiquinonyl (C),10e,g and trityl (D).10b hydrobromic acid. Condensation of the obtained salt of 2- 26100 | RSC