2-Hydroxy-4 , 6-dimethoxyacetophenone from Leaves of Peperomia glabella

A 2-hidroxi-4,6-dimetoxiacetofenona foi isolada de folhas de Peperomia glabella (família Piperaceae). A substância cristaliza no grupo espacial P — 1 com duas moléculas na unidade assimétrica. A análise estrutural revela uma rede bidimensional infinita no plano (011), estabilizada por ligações de hidrogênio inter-moleculares ao longo da direção [100] e interações de van der Waals ao longo da direção [011]. As moléculas apresentam fortes ligações de hidrogênio intra-moleculares [O1-HO1...O4 = 1,53(2) Å e O5-HO5...O8 = 1,38(2) Å]. A conformação molecular foi analisada usando o MOGUL, uma base de dados de geometria molecular derivada do CSD (Cambridge Structural Database).

The aim of the present work is to determine unambiguously the molecular structure of (1) by X-ray diffraction (XRD) and its intra and inter-molecular geometry as well.
To the best of our knowledge, this is the first occurrence of this class of compound in Peperomia species.

General Considerations
The compound was isolated from leaves of samples of Peperomia glabella.All chemicals used during the extraction, purification and crystallization were of analytical or chromatography grade.
1 H and 13 C NMR spectra (4.9 T) were recorded on a Bruker AC-200 spectrometer operating at room temperature, using tetramethylsilane as an internal reference.

X-ray Structure analysis of 2-hydroxy-4,6-dimethoxyacetophenone
A well-shaped single crystal of (1) was selected for the XRD experiments.The intensity data were collected at 150 K on an Enraf-Nonius Kappa-CCD diffractometer (95 mm CCD camera on k-goniostat) with graphite monochromated Mo Kα (λ = 0.71073 Å) radiation.The temperature was controlled using an Oxford Cryosystem low temperature device.Data collection (ϕ scans and ω scans with κ offsets) was made using the COLLECT; 32 integration and scaling of the reflections were performed with the HKL Denzo-Scalepack system of programs. 33The final unit cell parameters were based on all reflections using HKL Scalepack. 33The structure was solved using Direct Methods with SHELXS-97. 34The model was refined by full-matrix least-squares procedures on F 2 using SHELXL-97. 34H atoms of the phenyl and methyl groups were positioned stereochemically and were refined with fixed individual displacement parameters [U iso (H) = 1.2U eq (C aromatic ) or 1.5U eq (C methoxy )] using a riding model, with aromatic C-H distances of 0.95 Å and methyl C-H distances of 0.98 Å.The two hydroxyl H atoms were located by difference Fourier synthesis and were set as isotropic.
Data collections and experimental details for (1) are summarized in Table 1.The programs SHELXL-97, SHELXS-97, and ORTEP-3 35 were used within WinGX 36 to prepare materials for publication.The programs Mercury 37 and ORTEP-3 were used to prepare the molecular graphics.

Results and Discussion
Figure 1 shows an ORTEP-3 35 view of (1) with the atom numbering scheme.The structure crystallizes in P -1 with two independent molecules in the asymmetric unit (labelled as A and B in Figure 1).Comparison of these molecules by the method of Kabsch 38 showed them to be very similar with a root mean square deviation between homologous atoms of 0.024 Å.This fact suggested that the crystal could belong to a higher symmetric space group with just one molecule per asymmetric unit.Closer scrutiny, however, showed this is not the case because the affin transformation relating the two moieties did not coincide with any of those belonging to other space group.This symmetry was also carefully examined using PLATON, 39 and it was concluded that P -1 is in fact the correct space group.
The main geometric parameters are given in Table 2.The molecular conformation was analyzed using the MOGUL, 40 a knowledge base of molecular geometry derived from the Cambridge Structural Database (CSD) 41 that provides rapid access to information on the preferred values of bond lengths, valence angles and acyclic torsion angles.The Figure 2 shows an example of the graphical result of the query molecule studied here (molecule A).The resulting histogram is the C1-O1 bond length comparing with the C-O bond lengths in CSD entries containing similar structures.As emphasized by Bruno et al., 40 comparison of the dimensions of a newly determined small-molecule crystal structure with bond lengths and angles of similar structures in the CSD is useful as a check against refinement errors and to highlight unusual geometrical features.This study showed that all bond lengths and bond angles are in agreement with the expected values for a good X-ray diffraction structure refinement.However, the MOGUL analysis has pointed out two interesting geometrical features due to resonance involving the moiety O3-C5-C6-C7-O4 (see Figure 1 and Table 2).It was observed that C5-O3 and C6-C7 is shorter than the average query values whereas the C5-C6 and C7-O4 is longer than the expected ones.It is important to emphasize that the same behaviour (not shown in Table 2) was observed to the molecule B present in the asymmetric unit.
Both molecules in the asymmetric unit are almost flat.The largest deviations from the least squares plane through the aromatic ring system A are -0.176(4) and 0.112(4) Å for C8 and C9 atoms, respectively.Similar results were observed to the molecule B: the largest  deviations were observed to the C18 (-0.173(4)Å) and C19 (0.120(4) Å) atoms.The least squares planes of the A and B molecules form an angle of 0.8(1) o .This result shows that the two moieties are in the same plane, which is also illustrated in Figures 3 and 4.
The molecules A and B exhibited strong intra-molecular hydrogen bonds involving O1-HO1...O4 and O5-HO5...O8, respectively (Table 3 and Figure 1).The weak intermolecular hydrogen bond between the aromatic hydrogen linked to C4 (molecule A) and the adjacent carboxyl oxygen O1 at x+1, y, z stabilizes the packing of the molecule A and gives rise to an infinite one dimensional chain parallel to the [100] direction (Table 3, Figures 1 and 3).The same interaction occur to the molecule B involving the aromatic hydrogen linked to C14 (molecule B) and the adjacent carboxyl oxygen O5 at x+1, y, z.The chains form a planar structure, connected by van der Waals interactions along the [011] direction.Therefore, the chains are linked

2 )Figure 1 .
Figure 1.View of (1) with displacement ellipsoids for the non-hydrogen atoms shown at the 50% probability level.The H atoms are shown as spheres of arbitrary radii.Hydrogen bonds are indicated by dashed lines.

Figure 4 .
Figure 4. Packing of (1) projected onto bc plane.The separations between parallels infinite two-dimensional network parallel to the (011) plane are shown as dashed lines.

Figure 3 .
Figure 3. Packing of (1), showing the infinite two-dimensional network in the (011) plane.Hydrogen bonds are indicated by dashed lines.

Table 1 .
Crystal data, data collection details and structure refinement results of 1 -1 (No.