Synthesis and crystal structures of three Schiff bases derived from 3-formylacetylacetone and benzyl-, tert-butyl- and (S)-methylbenzylamine

The crystal structures of three Schiff bases synthesized from 3-formylaceylacetone and different primary amines were determined and compared with simulated gas phase structures based on DFT calculations.


Chemical context
3-Formylacetylacetone reacts with primary amines RNH 2 to give enamines with an amino-methylene-pentane-2,4-dione core. The first reference to this type of Schiff base compound dates back to Claisen, who used ethoxylideneacetylacetone as synthetic alternative to 3-formylacetylacetone. 3-Aminomethylene-pentane-2,4-dione, which may be regarded as the parent compound, was reported as early as 1893 (Claisen, 1893), and its crystal structure was reported in 2006 (Gró f et al., 2006a), almost simultaneously with that of the methylamino derivative (Gró f et al., 2006b). In 1966, Wolf & Jä ger. successfully used the deprotonation of 3-aminomethylenepentane-2,4-dione type Schiff bases to generate -iminoenolate chelate ligands, with special focus on tetradentate salen-type ligands (Wolf & Jä ger, 1966). In particular, these salen-type ligands have found broad application in the synthesis of Fe II complexes exhibiting spin-crossover effects (Dü rrmann et al., 2021). Moreover, the coordination properties of the iminoenolate ligands are conveniently modified by the introduction of additional donor groups. This is easily done by the reaction of 3-formylacetylacetone with a suitably functionalized amine, e.g. in form of -amino acids (Hentsch et al., 2014) or o-diphenylphosphinoaniline (Halz et al., 2021).
From the synthetic point of view it is worth mentioning that compounds 1 and 2 are also accessible by the ethoxylideneacetylacetone route (Zhou, 1997). Originally, compound 2 was obtained from a formimidoylation of acetylacetone with a substituted imidazole (Ito et al., 1974).

Structural commentary
Compounds 1 and 2 crystallize in the monoclinic system, space group P2 1 /c with Z = 4. Compound 3 forms monoclinic crystals in space group P2 1 with Z = 4. Both independent molecules in the asymmetric unit of 3 exhibit nearly identical bond lengths and angles.
In order to get some insight into how the observed conformations are influenced by crystal packing, the gas phase molecular structures of 1-3 were optimized by DFT methods using the Gaussian 16 program package (Frisch et al., 2016) at the B3LYP/TZVP/GD3BJ level of theory (Becke, 1993) with the implemented def2-TZVP basis set (Weigand & Ahlrichs, 2005) and dispersion correction GD3BJ (Grimme et al., 2011).
Bond lengths and angles of the calculated structures are in good agreement with the experimetal data. In Fig. 4, an overlay of the experimetal (blue) and the calculated structures (red) is shown. Obviously, the planar amino-methylenepentane-2,4-dione cores fit very well and most of the differences between experimental and theoretical structures are due       Hydrogen-bond geometry (Å , ) for 1.  Symmetry codes: (i) Àx þ 1; y þ 1 2 ; Àz þ 3 2 ; (ii) Àx þ 1; Ày; Àz þ 1. Table 6 Hydrogen-bond geometry (Å , ) for 3. to the conformations of the organyl groups attached to the enamine nitrogen atom. Table 7 represents a comparison of experimental and calculated torsion angles at the C7-N bond. In the case of compounds 1 and 2, there is only a moderate increase of the torsion angles with respect to the theoretical values. Addi-tionally, compound 1 exhibits a small change in the orientation of the phenyl group (Fig. 4a). In the case of compound 3, the conformational effects are more pronounced and the torsion angles are increased by around 73 . Moreover, the orientation of the phenyl group is also affected (Fig. 4c).
In the case of compound 1 there is a C11 (5) type C-HÁ Á ÁO hydrogen bridge between the enamine CH group (C6-H7) and the acetyl O atom (O2) of of a neighboring molecule (Table 4, Fig. 8). This leads to helical chains that propagate in the direction of the c axis. Moreover, the packing of the helices is supported by weakinteractions [3.8747 (12) Å between the centroids of the phenyl groups, 3.79 Å between C3 of the (amino)methylene-pentane-2,4-dione unit and the centroid of the phenyl ring and 3.42 Å between neighboring (amino)methylene-pentane-2,4-dione units]. As a result, ribbons extending parallel to [001] are formed, Figs. 9, 10.
The Hirshfeld plot of compound 2 reveals that each molecule is involved in four C-HÁ Á ÁO hydrogen bridges between t-butyl groups and acetyl oxygen atoms of neighboring molecules (Fig. 6)  View of the Hirshfeld surface of 1 mapped over d norm in the range À0.712 to 0.973 au, showing intermolecular hydrogen bonds as green dashed lines.

Figure 6
View of the Hirshfeld surface of 2 mapped over d norm in the range À0.712 to 0.973 au, showing intermolecular hydrogen bonds as green dashed lines.

Figure 7
View of the Hirshfeld surface of molecule 1 of compound 3 mapped over d norm in the range À0.712 to 0.973 au, showing intermolecular hydrogen bonds as green dashed lines. Table 7 Comparison of torsion angles in the crystal structures of 1-3 and from theoretical DFT calculations.

Compound Torsion angle
Crystal structure determination DFT calculation *Values for the comparable bond in the second molecule.

Figure 8
Section of the crystal structure of 1 showing the hydrogen bond.
Compound 3 exhibits two major types of interactions that are based on C-HÁ Á ÁO hydrogen bridges (Table 6) and C-HÁ Á Á contacts with an HÁ Á ÁCg(phenyl) distance of 2.68 Å . The C-HÁ Á ÁO hydrogen bridges are formed between methyl and phenyl groups of the methylbenzyl residue as donors and acetyl oxygen atoms of neighboring molecules as acceptors ( Fig. 12). In the case of the C-HÁ Á Á interaction, the benzyl CH fragment and a neighboring phenyl group are involved ( Fig. 13,  Helical chains of 1 stabilized by hydrogen bonds (thin dashed lines) and interactions.

Figure 11
Stacking of the molecules in 2 along the [001] direction.
A comparison of the calculated gas phase structures and the experimentally determined structures reveals that the effect of crystal packing is only marginal for compounds 1 and 2, i.e. only minor adjustments of the molecular conformations are required for optimum intermolecular interactions. In contrast to these compounds, 3 requires a stronger molecular reorganization in the solid state and presumably this is in particular due to C-HÁ Á Á interactions.

Synthesis and crystallization
3-Formylacetylacetone (3.00 g, 23.4 mmol) and the corresponding amine [1.76 g of benzylamine for 1, 2.57 g of tertbutylamine for 2 and 2.91 g of (S)-methyl-benzylamine for 3, 24.0 mmol] were dissolved in methanol (50 ml) and heated under reflux for one h. After removal of the volatiles in vacuo, the residue was washed twice with cold n-pentane and afterwards dried in vacuo.
Crystals suitable for single-crystal X-ray diffraction were obtained by slow evaporation of the solvent from solutions in methanol (compounds 1 and 3) or diethyl ether (compound 2

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 8. Hydrogen atoms were positioned geometrically (C-H = 0.95-0.98 Å ) and refined as riding, with U iso (H) = 1.2U eq (C) for CH and NH hydrogen atoms and U iso (H) = 1.5U eq (C) for CH 3 hydrogen atoms. The investigated crystal of 3 was twinned by non-merohedry and treated as a two-domain crystal with a refined BASF factor of 0.1151.

3-[(Benzylamino)methylidene]pentane-2,4-dione (1)
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.

3-[(tert-Butylamino)methylidene]pentan-2,4-dione (2)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.30 e Å −3 Δρ min = −0.14 e Å −3 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.

3-{[(S)-Benzyl(methyl)amino]methylidene}pentane-2,4-dione (3)
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 twin.