Intermolecular hydrogen bonding in N-methyl-N′-(pyridin-2-yl)benzene-1,2-diamine

Unexpected dual intermolecular hydrogen bonding has been observed in a class of N-aryl-substituted ortho-phenylene diamine compounds. Initially detected in solution by the observation of unexplained signals in the 1H NMR spectrum, it was further corroborated by two-dimensional COSY NMR spectroscopy and solid-state X-ray crystallography data.


Chemical context
ortho-Phenylene diamine compounds are valuable precursors that have widespread use in a number of applications, especially as carbene ligands (Peris, 2018;Flanigan et al., 2015;Hopkinson et al., 2014;Fè vre et al., 2013;Velazquez & Verpoort, 2012;Doddi et al., 2019). The synthesis of orthophenylene diamine derivatives, whether it be introducing functionality on the aryl ring or the nitrogen atom of the amine group, remains a challenge and continues to attract ongoing efforts to develop efficient synthetic routes to access a diverse library of functionalized compounds. We have been interested in functionalized symmetrical and unsymmetrical ortho-phenylene diamine derivatives to access organometallic compounds for use in catalysis applications (Wang et al., 2013) and novel azaborole systems (Abbey & Liu, 2013;Weber, 2012Weber, , 2008Segawa et al., 2009). Although a number of symmetrical ligands, such as I and II, are readily available commercially, unsymmetrical ligands, such III and IV, are less common because the chemical routes and purification processes to access these compounds are more complicated (substituted ortho-phenylene diamine compounds I-VI of interest are shown in the scheme below).
Compound IV was synthesized by a modification of a literature procedure (Wang et al., 2013). Analysis of the compound using 1 H NMR spectroscopy to confirm the purity revealed some unexpected findings (see supporting information) when compared with similar compounds shown in the scheme. Upon initial purification and isolation of IV, analysis by proton NMR in CDCl 3 sometimes showed what seemed to be two different methyl signals, which we initially assumed was a contaminant originating from the reaction that could not be easily removed. However, analysis of the same material by 13 C NMR spectroscopy showed a relatively simple and clean spectrum, suggesting signals for only a single compound or, if a second compound was present, the signals could be overlapping and therefore difficult to distinguish. Previously reported compounds I and II are both symmetrical and show very simple and expected signals in their respective 1 H NMR spectra (see Figs. S1 and S2). The methyl signal of I was found as a singlet at 2.9 ppm and NH protons as a broad singlet at 3.0-3.5 ppm. Meanwhile, compound II shows the NH protons occurring as a broad singlet further downfield at 5.5-5.7 ppm, presumably caused by deshielding effects of the aryl substituents. Analysis of compound IV in CDCl 3 shows well-defined signals that can be attributed to the aryl and pyridyl protons occurring in the downfield region between 6.3-8.3 ppm region (Fig. S3). The methyl signal occurs at 2.85 ppm, and it is interesting to see two different types of NH protons, a broad singlet at 4.1-4.5 ppm and a broad multiplet at 6.2-6.3 ppm. While we expect the chemical environments to be significantly different for the NH protons, we were unable to explain the multiplet-nature or coupling of these NH protons to another proton spin system. To further probe these unusual spectroscopic features, proton NMR analysis was undertaken in d 6 -DMSO (Fig. S4), which resulted in significant sharpening of the NH signals. The initial broad NH peak now appears as a broad multiplet around 5 ppm, and the methyl signal is split into a second order doublet, which was very unexpected. 2D COSY spectroscopy in d 6 -DMSO was performed on the same NMR sample (Fig. 1) and clearly showed the upfield NH multiplet at 5 ppm to be directly coupled through the nitrogen atom with the neighbouring protons on the methyl group. On the NMR time scale, proton-to-methyl coupling through the nitrogen atom is never reported as the NH proton is extremely labile (i.e. evident by very broad or even undetectable signals in proton NMR spectra) and readily undergoes facile exchange: to the best of our knowledge this type of NH proton coupling is exceptionally rare. In addition, the other downfield NH proton has sharpened further in d 6 -DMSO and appears as a multiplet at 6.4-6.5ppm, which suggests this NH proton may be involved in longer range coupling of the protons in the pyridyl ring. From the COSY spectrum, it appears that this NH proton is involved in long-range coupling with the pyridyl and/or phenyl protons. To understand the cause of this unexplained coupling observed in the 1 H NMR spectra for compound IV, analysis by X-ray crystallographic methods was undertaken.

Structural commentary
The molecular structure and atom-numbering scheme of the title compound is shown in Fig. 2. The asymmetric unit comprises two independent molecules assembled in a selfcomplementary N-HÁ Á ÁN hydrogen-bonded dimer with a classical ring motif ( Table 1). The overall configuration of the N 0 -(2-pyridyl)-benzene-1,2-diamine core of the molecule is very similar to that observed in the closely related compound, N-(2-bromobenzyl)-N 0 -(2-pyridyl)-benzene-1,2-diamine Molecular diagram of the title compound, with non-hydrogen atoms represented by 50% displacement ellipsoids and hydrogen atoms as spheres of arbitrary size.

Figure 1
Two-dimensional COSY spectrum of N-methyl-N-phenyl-1,2-diaminobenzene, IV (d 6 -DMSO). Table 1 Hydrogen-bond geometry (Å , ). (3) 3.337 (2) 142 (2) (Manjare et al., 2009). The angles between the mean planes of the pyridyl and o-diaminophenyl rings are 61.80 (10) and 62.33 (10) for molecules I and II, respectively. In this configuration, the second N-H moiety on each molecule is sufficiently close to the opposing pyridyl nitrogen atom, resulting in two further but much weaker N-HÁ Á ÁN interactions (Table 1). Notably, the equivalent DÁ Á ÁA distances in Similarly, the C-N bonds associated with the second amine group display the same variation with shorter distances to the aryl-amine fragment and longer to the methyl group. Solution and solid-state structural studies of substituted 2-arylamino-pyridine derivatives indicate that these molecules can form two different stable conformations through rotation of the aryl ring about the C-N bond (Takasuka et al., 1986). In one conformation, the pyridyl and aryl rings are not coplanar, whereas in the alternate conformation the two rings are co-planar, with an intermolecular C-HÁ Á ÁN interaction between the pyridyl nitrogen atoms and the 2-aminoaryl ring. The former leads to dimer formation such as observed for the parent compound 2-(phenylamino)pyridine (Polamo, et al., 1997) and in the current example. In contrast, the latter conformation may lead to alternate structural motifs such as 1-D catemer chains (Talja & Polamo, 2005;Polamo & Talja, 2004) or interactions with other functional groups (Takasuka et al., 1986). The structure of N,N 0 -bis(2-pyridyl)benzene-1,2diamine shows both conformations in a single molecule (Gdaniec et al., 2004).

D-HÁ
Of greater interest is compound VI, which is very similar to our current compound IV. While compound VI contains the bulky 2-bromo-benzyl group attached to one amino group, it still forms the hydrogen-bonded dimer V complex. The reported proton NMR spectrum of V in CDCl 3 (Manjare et al., 2009) reveals some interesting features that are similar to those of compound IV. The methylene protons on VI are magnetically non-equivalent whereby each proton has a different chemical shift of 4.83 and 4.41 ppm and are strongly coupled to each other. The two NH protons are also in different environments, one located downfield at 6.15 ppm as a multiplet and the other lies under a methylene proton signal at 4.41 ppm, which are essentially in the same location as for compound IV. Interestingly, as compound VI is only analysed in CDCl 3 , the authors do not observe any coupling of the NH proton with either of the methylene protons. We suspect the CH 3 -NH coupling observed in IV when using CDCl 3 is less pronounced or enhanced by solvation effects than when using d 6 -DMSO. Nevertheless, the presence and observation of this CH 3 -NH coupling in compound IV, to the best of our knowledge, is rare, and in this case a result of the dual intermolecular hydrogen bonding, occurring from the primary amino-pyridine dimer complex and secondary pyridyl and CH 3 -NH interaction.

Synthesis and crystallization
N,N 0 -Dimethyl-1,2-phenylenediamine I and N,N 0 -diphenyl-1,2-phenylenediamine II were obtained from commercial sources, while compound IV was synthesized following modification of a literature procedure (Wang et al., 2013). Interestingly, compounds I and II are liquids and discolour easily, possibly due to the presence of residual contaminants that may be difficult to remove completely during purification. This can make purification of the ligand difficult when the R groups are small (i.e. methyl). Introduction of bulky aryl groups provides materials that are crystalline and can be purified easily by chromatography and recrystallization. Compound IV was synthesized by methylation of commercially available N-(pyridin-2-yl)benzene-1,2-diamine by modifying literature conditions (Wang et al., 2013) to introduce the methyl group onto the primary amine functionality. This compound was purified by chromatographic methods to afford a white solid in high purity. A suitable sample for X-ray determination was achieved by the slow diffusion of petroleum ether into a solution of IV dissolved in ethyl acetate.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The structure was solved in the non-centrosymmetric space group Pna2 1 and refined as a racemic twin [BASF 0.3 (5)]. Hydrogen atoms attached to carbon were placed in calculated positions and refined using a riding model. The hydrogen atoms of the NH groups were located in a difference-Fourier map, and freely refined.

Funding information
Funding for this research was provided by: CSIRO Manufacturing Flexible Electronics Theme as part of the OLED research program.

N-methyl-N′-(Pyridin-2-yl)benzene-1,2-diamine
Crystal data Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refined as a 2-component inversion twin.