The synthesis of new functionalized 1,3,5-triazine-based stable bi-and trinitroxides of the 2,5-dihydroimidazole series

New non-conjugated functionalized 2,5-dihydroimidazole-type bi-and trinitroxyl radicals are described. The synthesis of which was based on a nucleophilic substitution reaction between 2,4,6-trichloro-1,3,5-triazine or 2,4-dichloro-6-methoxy-1,3,5-triazine and spiro-fused 2,5-dihydroimidazole-type monoradicals bearing both a p-hydroxyaryl moiety at the C-4 atom of the heterocycle and a residue at the fourth position of the cyclohexane ring. The model tris-nitroxide with an unsubstituted cyclohexane unit was structurally characterized in the solid state.


Introduction
Trisubstituted 1,3,5-triazines represent a rapidly developing class of organic compounds.Due to their symmetrical structure and self-organized ability to form ordered media as well as good thermal stability, striazines are useful in materials science and manifest a wide range of practical characteristics such as nonlinear optical 1,2 and liquid crystalline [3][4][5][6][7][8] properties including photoluminescence. 9In addition, triazine derivatives were recently proved to be stable molecular glasses highly resistant to crystallization, 10 promising inhibitors of organic corrosion of steel in acids, 11 and unique scaffolds in the synthesis of highly efficient covalent organic frameworks (COFs) applied to photocatalytic hydrogen production. 12agnetic liquid crystals (LCs) attract a great deal of attention because they may engage in unique magnetic interactions and have unconventional magneto-electric and magneto-optical properties. 13Over the last decade, stable organic radicals such as pyrrolidine-type nitroxides (PROXYLs), 14,15 trityls, 16 verdazyls, and benzo[e] [1,2,4]triazinyls (Blatter's radicals) [17][18][19][20] were used to designing all-organic paramagnetic calamitic, discotic, and bent-core LCs.][19][20] In this regard, the synthesis of new paramagnetic all-organic liquid crystalline bi-and triradicals containing nitroxide moieties inside the lateral heterocyclic 2,5-dihydroimidazole skeleton as spin sources and a central 1,3,5-triazine core as a robust linker seems to be promising.Besides, an s-triazine core may be a useful template for elaborating synthetic approaches to various disjoint hetero-di-and triradicals containing paramagnetic nuclei of different structural types.

Results and Discussion
To synthesize paramagnetic compounds 1a-c and 2a-c, we applied a nucleophilic substitution reaction of cyanuric chloride or 2,4-dichloro-6-methoxy-1,3,5-triazine and the corresponding derivatives of spirocyclic 2,5dihydroimidazole-type monoradicals 3, 34 4, and 5 containing a 4-hydroxyaryl residue in the presence of a base (Figure 2).In this regard, first, we describe the preparation and structural characterization of novel nitroxides 4 and 5.  5) 35 possessing a protected phenolic group proceeded with high stereoselectivity and quantitatively led to a single isomer of 7. The stereochemistry of 7 was determined by comparing its 1 H and 13 C NMR spectra with those recorded for compound 8.In our previous publication, 8 was found to have a trans-ee-configuration. 36 Because the corresponding chemical shifts and coupling constants (see the Experimental section) of 7 were identical to those obtained for debenzylated analogue 8, we assigned the structure of a trans-ee-isomer to 7. Oxidation of hydroxylamine 7 with manganese dioxide in chloroform gave nitroxide 9 with an 80% yield.As already mentioned, tris(alkyloxy)benzoic acid derivatives can have LC properties and show columnar mesophases, 6 as such, we added this mesogenic residue to our nitroxide radicals.Thus, acylation of nitroxide 9 by 3,4,5-tris(dodecyloxy)benzoic acid under Mitsunobu reaction 37 conditions allowed us to obtain the desired acylated derivative 10 with a high yield.Debenzylation of ester 10 by hydrogenation on a palladium catalyst was always accompanied by a side reaction of reduction of the nitroxyl function to a cyclic hydroxylamine.Oxidation of the intermediate imidazoline by MnO 2 in CHCl 3 produced target nitroxide trans-4 containing a phenolic group with a moderate yield (Scheme 1).Scheme 1.The synthesis of phenolic-group-containing nitroxide trans-4.
The synthesis of the next paramagnetic phenol 5 was started from spiro-fused derivative 11 prepared as a diastereomeric mixture by a previously described synthetic procedure. 35The subsequent Mitsunobu acylation reaction with 3,4,5-tris(dodecyloxy)benzoic acid and separation of obtained isomers cis-12 and trans-12 by preparative thin-layer chromatography (TLC) on silica gel afforded the individual compounds cis-12 and trans-12 in the ratio 5.7:1.0.To confirm the spatial structure of the obtained isomers, they were reduced in aqueous tetrahydrofuran (THF) to the corresponding diamagnetic N-hydroxy derivatives cis-13 and trans-13 by means of a Zn/NH 4 Cl system.A comparison of 1 H and 13 C NMR spectra of cis-13 and trans-13 (see the Experimental section and Supporting Information) with those of previously described analogues cis-14 and trans-14 35 allowed us to identify their stereochemistry, as depicted in Scheme 2. Subsequent hydrogenation of both isomers on the palladium catalyst followed by oxidation with MnO 2 in CHCl 3 led to the desired 4,5dihydroimidazole derivatives cis-5 and trans-5 in moderate yields.Given that the overall yield of minor isomer trans-5 was very low, we did not subject this compound to further transformations; only isomer cis-5 was used in the next synthetic step.
The final step of our synthesis was the nucleophilic substitution of chlorides from cyanuric chloride and 2,4-dichloro-6-methoxy-1,3,5-triazine, respectively via a reaction with the synthesized paramagnetic phenols.At first, we tried to carry out this reaction with compound 3, which has no substituents at position 4 of the cyclohexane ring.Because radical 3 does not contain lipophilic groups (long alkyl chains), it was possible to generate its phenolate anion in an alkaline aqueous solution.The interaction of 3 or 2 molar equivalents of this anion with 1,3,5-trichlorotriazine or 2,4-dichloro-6-methoxy-1,3,5-triazine successfully produced the corresponding tri-and biradicals 1a and 2a in 80 and 75% yields, respectively (Scheme 3).Scheme 3. The synthesis of target tri-and biradicals 1a and 2a.
The crystal structure of triradical 1a was determined by the X-ray diffraction method (Figure 3).The molecules of 1a are located on threefold rotational axes and have Δ-conformations inside the crystal. 38At the same time, phenoxy moieties of each molecule are almost perpendicular to the plane of the triazine core [torsion angle C1-O1-C2-C3: 83.4(2)].An analogous orientation of phenoxy groups is observed, for example, in a solvate of 2,4,6-tris(4-bromophenoxy)-1,3,5-triazine with hexamethylbenzene. 39The geometry of the 3phenyl-1,4-diazaspiro[4.5]dec-3-ene 1-oxyl moiety is almost similar to that in 2,2-dimethyl-3-[4-(decyloxy)phenyl]-1,4-diazaspiro[4.5]dec-3-ene1-oxyl. 34The dihedral angle between the phenyl and 2,5-dihydroimidazole planes is 4.2(2).It is worth noting that the formed layers are parallel to the ab plane owing to the C6-H…O2 interaction (the H…O distance: 2.38, the C-H…O angle: 140) in the crystal packing of triradical 1a.Moreover, inside and between the layers, there are some voids, which are filled with highly disordered solvent molecules (see the Experimental section).Because we could successfully realize the coupling between unsubstituted paramagnetic derivative 3 and 1,3,5-trichlorotriazine as well as 2,4-dichloro-6-methoxy-1,3,5-triazine, we tried to conduct the same reaction with more complex and encumbered nucleophiles, such as radicals trans-4 and cis-5.Given that these compounds contain lipophilic groups, it was impossible to obtain their phenolate anions in an alkaline aqueous solution.For this reason, we chose potassium carbonate in acetone as a base medium.Because of the relatively weak basicity of the medium, boiling the mixture containing cyanuric chloride, trans-4, or cis-5 and potassium carbonate in acetone within 5 h gave the mixture of target triradicals 1b or 1c, respectively along with disubstitution products: diradicals 15b and 15c in the ratio 2:1 with an overall yield of ~60%.On the other hand, such reaction incompleteness makes it in principle possible to obtain mono-and disubstitution products under the experimental conditions.The interaction between 2,4-dichloro-6-methoxy-1,3,5-triazine and nitroxides trans-4 and cis-5 enabled obtaining desired biradicals 2b and 2c, respectively with a 45% yield.S1 (see the Supporting Information).None of the compounds possesses liquid crystalline properties.Trans-4, trans-5 and cis-5 represent pale-yellow amorphous solids and showed only crystal-to-crystal and crystal-to-isotropic liquid phase transitions.1b,c, 2b,c and 15b,c are pale yellow waxy solids and showed no peaks in differential scanning calorimetry (DSC) curves in the temperature interval from 25 to 140 C.When the starting temperature was decreased to -10 C the corresponding melting peaks appeared at the temperatures lower than 25 C (see Table S1).No birefringent texture was observed for all the compounds by optical polarizing microscope if the temperature was higher than their melting point in the heating and in the cooling runs.It was assumed that they do not possess liquid crystalline properties as a consequence of low space fill factors of such bulky molecules.

Conclusions
We developed a convenient approach to the synthesis of stable 1,3,5-triazine-based bi-and triradicals of the 2,5-dihydroimidazole series.Six new bi-and tris(nitroxides) were obtained, and symmetrical nature of the model tris(nitroxide) was confirmed by single crystal X-ray diffraction analysis.Investigation of the bi-and tris(nitroxides) containing mesogenic groups by means DSC and optical polarizing microscope revealed that none of synthesized radicals possess LC properties.Nevertheless, the proposed conditions for the nucleophilic substitution of chloride from cyanuric chloride with paramagnetic phenols allow us to expect successful syntheses of new hetero bi-and triradicals containing various structural types of paramagnetic units.

X-Ray crystallography
The X-ray single-crystal diffraction data for triradical 1a were collected at 200 K on a Bruker Kappa APEX II instrument with MoKα radiation (λ = 0.71073 Å) and a CCD area detector.The structures were solved by direct methods in the SHELXS software and refined on F 2 using all the data by full-matrix least-square procedures in SHELXL-97.Multiscan absorption corrections were performed in the SADABS software.The positions of nonhydrogen atoms were refined with anisotropic displacement parameters.All hydrogen atoms were included in the calculated positions with isotropic displacement parameters at 1.2 times the isotropic equivalent of their carrier atoms.The guest molecules of hexane and EtOAc are strongly disordered and located next to the threefold and rotoinversion threefold axes.Therefore, the SQUEEZE function in PLATON was employed to calculate the potential solvent-accessible area in the unit cell; 3×396 and 3×140 Å 3 were calculated containing approximately 3×106 and 3×37 electrons.Accordingly, the first three voids may contain six solvent molecules (hexane/EtOAc), and the next three voids may contain water or be empty.

Figure 3 .
Figure 3.An ORTEP drawing of triradical 1a with 30% probability of ellipsoids.Atom labels are shown only for the asymmetric part of the molecule.