Synthesis and crystal structures of three new benzotriazolylpropanamides

The crystal structures of benzotriazolylpropanamides are governed by π–π stacking between the benzotriazolyl residues and, in the case of primary amide NH2 groups, by N—H⋯O and N—H⋯N bridging.


Chemical context
Di-and tridentate pyrazolyl-based ligands play an important role in the design of supramolecular assemblies of metal complexes. Particularly notable among the large variety of such ligands are Trofimenko's famous poly(pyrazolyl)borates ('scorpionates') (Trofimenko, 1993(Trofimenko, , 2004Marques et al., 2002;Paulo et al., 2004;Smith, 2008) and the poly(pyrazolyl)methane ligands (Bassanetti et al., 2016;Bigmore et al., 2005;Krieck et al., 2016;Otero et al., 2013;Semeniuc & Reger, 2016). In a series of previous studies, we reported the synthesis and supramolecular coordination chemistry of the simple, functionalized pyrazolyl-based ligand 3-(pyrazol-1-yl)propanamide. This ligand is readily available in one step via basecatalyzed Michael addition of pyrazole to acrylamide (Girma et al., 2008). In combination with various first-and second-row transition metals (e.g. Mn, Fe, Ru, Co, Ni), 3-(1H-pyrazol-1yl)propanamide allows the design of a variety of hydrogen-bonded supramolecular assemblies, including different chains, sheets, and three-dimensional arrays (D'Amico et al., 2015). As an additional advantage, the pyrazolylpropanamide ligand system can be easily modified either by attachment of substituents to the propanamide backbone (D'Amico et al., 2015) or by replacing the pyrazole ring by other N-heterocycles such as triazole (D'Amico et al., 2015;Wagner et al., 2012). In our most recent study, we investigated the structural influence of benzotriazolyl as a hydrophobic functional group, which imparts amphiphilic character to the ligand and forms the basis of novel supramolecular assemblies. In the course of this work, the solid-state structures of 3-(1H-benzotriazol-1yl)-propaneamide (= 'BTPA') and of several first-row transition metal complexes (Mn, Co, Cu) derived thereof have been described (Wang et al., 2017). We report here the synthesis and structural characterization of three new potentially useful benzotriazolylpropanamide ligands.
The title compounds were prepared by base-catalyzed Michael addition of benzotriazole to methyl-substituted acrylamides, namely 2-methylacrylamide and N,N-dimethylacrylamide. As shown in the reaction scheme ( Fig. 1), benzotriazole exists in two tautomeric forms A and B. Spectroscopic data (UV, IR and 1 H NMR) (Negri & Caminati, 1996;Nesmeyanov et al., 1969;Poznań ski et al., 2007) and dipole moment measurements (Mauret et al., 1974) revealed that the 1H-tautomer A is the predominant species at room temperature.
The thermal reaction of benzotriazole with 2-methylacrylamide was carried out in the usual manner (D'Amico et al., 2015;Wagner et al., 2012;Wang et al., 2017) in the presence of Triton B (= benzyltrimethylammonium hydroxide) as basic catalyst. Repeated recrystallization of the crude product from ethanol afforded 3-(1H-benzotriazol-1-yl)-2-methylpropanamide (1) in 32% isolated yield. The compound was characterized through elemental analysis as well as IR and NMR ( 1 H, 13 C) spectroscopy. In the 13 C NMR spectrum, the amide carbonyl C atom gives a characteristic resonance at 175.2 ppm. The formation of 1 as the main reaction product corresponds to the predominant presence of tautomer A in the starting benzotriazole. From the mother liquor of the recrystallization of 1, a small amount of colorless crystals could be isolated, which were found to be the isomer 3-(2H-benzotriazol-2-yl)-2methylpropanamide (2) resulting from the reaction of the 2Htautomer B with 2-methylacrylamide. Compound 2 could also be fully characterized by elemental analysis as well as IR and NMR data.
In a similar manner, a reaction of benzotriazole with neat N,N-dimethylacrylamide in the presence of Triton B afforded a yellow oil which was shown to be an approximate 2:1 mixture of 3 and 4. Once again, the main component was the Michael addition product resulting from the 1H-tautomer A of benzotriazole. Thus far, only isomer 3 could be isolated in pure form by recrystallization of the oily crude product from ethanol. The identity of 3-(1H-benzotriazol-1-yl)-N,N-dimethylpropanamide 3 was confirmed by elemental analysis and spectroscopic data (IR, 1 H and 13 C NMR). In the 13 C NMR spectrum, the NMe 2 group gives rise to two resonances at 33.2 and 35.5 ppm, whereas the signal of the amide carbonyl C atom is found at 169.5 ppm.  The molecular structure of 1 in the crystal. Displacement ellipsoids are drawn at the 50% probability level.

Figure 3
The molecular structure of 2 in the crystal. Displacement ellipsoids are drawn at the 50% probability level.

Figure 4
The molecular structure of 3 in the crystal. Displacement ellipsoids are drawn at the 50% probability level. The methyl group C11 shows rotational disorder over two orientations (only one orientation of the H atoms is shown).

Structural commentary
Compounds 1-3 exist as well-defined monomeric molecules in the crystal, without any solvent of crystallization . The C O separations are in a narrow range around 1.24 Å and are therefore virtually equal with those observed in related functionalized propanamides (Girma et al. 2008;Wagner et al. 2012;D'Amico et al. 2015;Wang et al. 2017). Thus, the C O distance is not markedly influenced by hydrogen bonding, as there are N-HÁ Á ÁO bridges in 1 and 2, but not in 3 (see Supramolecular features section). The same applies to the amide C-N separation, which is around 1.33 Å in all compounds. The torsion angle C1-C2-C3-N between the amide group and the 1H-benzotriazol-1-yl residue is 71.0 (1) (1) and À72.2 (2) (3), respectively, which is close to the value observed in the unsubstituted BTPA (71.3 (1) ; Wang et al., 2017). By contrast, the same torsion angle in the 2H-benzotriazole-derived compound 2 is considerably smaller at 59.7 (1) .

Figure 6
The unit cell of 1, illustrating the aggregation of the chains shown in Fig. 5 bystacking into a three-dimensional framework, viewed in a projection on (010).

Figure 7
Supramolecular chain of rings in 2, formed by N-HÁ Á ÁO and N-HÁ Á ÁN bridging, extending along the crystallographic a axis.
centroids is 3.655 (2) Å , which is in the range of strong interactions (McGaughey et al., 1998). The so-formed dimers are interconnected by another interaction to an infinite chain, where an attractive interaction seems to exist between the whole bicyclic C 6 N 3 system rather than between the C 6 rings only (cf. Fig. 10c). The closest intermolecular separations are 3.308 (2) Å (C9Á Á ÁN2) and 3.403 (2) Å (C5Á Á ÁC10), and therefore in the same range as in the former mentioned interaction. In the case of 2, a layer structure parallel to (001) is formed (Fig. 8). The geometry of the interaction between the C 6 rings is similar as in 1, but the closest CÁ Á ÁC contact exists between C5 and C9 with 3.521 (2) Å , and the corresponding separation between the C 6 centroids is considerably larger at 3.933 (2) Å (cf. Fig. 10b). In 3, only two molecules are stacked together to a simple dimer ( Fig. 9), with participation of the whole C 6 N 3 bicycle similar as described above for 1 (cf. Fig. 10c). Here, the closest intermolecular contacts are 3.468 (2) Å (C8Á Á ÁN2) and 3.509 (2) Å (C4Á Á ÁC9), which is significantly larger than in 1. Comparable interactions as in 1-3 have not been observed in the unbridged BTPA, but in its metal complexes [MCl 2 (BTPA) 2 ] (M = Mn, Co, Cu; min. CÁ Á ÁC 3.45 Å ; Wang et al., 2017). The arrangement of the benzotriazolyl groups in the latter compounds is similar to that in 3 (cf. Fig. 10c).

Synthesis and crystallization
All manipulations were performed under inert nitrogen or argon atmospheres using standard Schlenk techniques or in a Vacuum Atmospheres Glove Box. The starting materials were obtained from commercial sources and used as received. Solvents were dried using an Innovative Technology, Inc, solvent purification system. Microanalysis was performed by Galbraith Laboratories, Inc, Knoxville, TN, USA. NMR spectra were obtained using Bruker Avance 300 MHz and 400 MHz NMR Spectrometers. IR spectra were recorded using KBr pellets with a ThermoNicolet Avatar 370 FT-IR between 4000 cm À1 and 400 cm À1 .

Figure 8
The unit cell of 2, illustrating the aggregation of the chains shown in Fig. 6 bystacking, to a two-dimensional array extending parallel to (001), viewed in a projection on (100).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. All H atoms were fixed geometrically using a riding model with U iso (H) = 1.2 U eq (X) (X = C, N). The CH 3 groups were allowed to rotate freely around the C-X vector (X = C, N) (AFIX 137 in SHELXL), and the amide NH 2 groups in 1 and 2 were constrained to be planar (AFIX 93 in SHELXL). C-H distances in CH 3 groups were constrained to 0.98 Å , those in CH 2 groups to 0.99 Å and those in CH groups to 1.00 Å . N-H distances in 1 and 2 were constrained to 0.88 Å . For compound 2, reflection (562) strongly disagreed with the structural model and was therefore omitted from the refinement. In the case of compound 3, one N-bonded methyl group (C11) was refined as rotationally disordered over two positions. Site occupancy factors were refined freely to 0.59 (2) for H12A, H13A and H14A, and to 0.41 (2) for H12B, H13B and H14B.  (2), (3). Program(s) used to solve structure: SHELXS97 (Sheldrick, 2008) for (1), (2); SIR97 (Altomare et al., 1999) for (3). For all compounds, program(s) used to refine structure: SHELXL2016 (Sheldrick, 2015); molecular graphics: DIAMOND (Brandenburg, 1999); software used to prepare material for publication: SHELXL2016 (Sheldrick, 2015). where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.33 e Å −3 Δρ min = −0.21 e Å −3 Extinction correction: SHELXL2016 (Sheldrick, 2015), Fc * =kFc[1+0.001xFc 2 λ 3 /sin(2θ)] -1/4 Extinction coefficient: 0.0117 (12) 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.