Synthesis X-ray Structure of a New Pyrrolo[1,2-b]-pyridazine Derivative

The synthesis, characterization and X-ray crystal structure of 2-(4-chloro-phenyl)-7-methylpyrrolo[1,2-b]pyridazine are reported. The compound crystallizes in the space group P21/c (No.14) with a =3.8568(1), b = 11.0690(3), c = 26.4243(7) Å, β = 92.777(1)° and Z = 4. Accurate molecular parameters for the novel heterocyclic system were obtained from intensity data collected at 113K. The molecule assumes a planar conformation in the crystal and the packing is based on π-π stacking with interplanar spacing 3.400 Å, typical of aromatic molecules with potential for displaying useful optical properties.


4
As suggested [2], the expansion of the π-electron system could have strong influences on the fluorescent properties of the compounds under discussion and represents the key step in the design of novel optically active materials. It is also known that π-π stacking interactions in the solid state are needed in order to have an extended π system, thus enabling electron mobility in the material. Such interactions are present in conjugated planar structures and to verify this hypothesis, the X-ray structure of 4 was determined.

Results and Discussion
2-(4-Chlorophenyl)-7-methylpyrrolo[1,2-b]pyridazine (4) was prepared from the ester 2 [11], under basic conditions, followed by thermal decarboxylation of the corresponding acid 3. The structure of the pyrrolo[1,2-b]pyridazine 4 was confirmed by elemental analysis and NMR spectroscopy. In its 1 H-NMR the methyl group (δ = 2.62 ppm) appeared as a doublet (J = 0.7 Hz) due to the coupling with H-6. The H-5 proton (δ = 6.67 ppm) appeared as a doublet with coupling constant J = 4.3 Hz, whereas H-6 (δ = 6.47 ppm) gave a double quartet with coupling constants of 4.3 and 0.7 Hz corresponding to the coupling with H-5 and methyl protons. The H-3 and H-4 protons from the pyridazine moiety gave two doublets at 6.82 and 7.72 ppm (J = 9.3 Hz). Also, the protons from the benzene ring appeared as two doublets with J = 8.6 Hz.
The 13 C-NMR data for compound 4 were in agreement with the structure assignment. The chemical shifts of tertiary carbon atoms were established by the HETCOR experiment. In turn, the chemical shift from 148.2 ppm was attributed to the C-2 atom due to its vicinity with the N-2 atom. Figure 1 shows the molecular structure of 4 in the crystal. The maximum deviation of any atom from the least-squares (LS) plane including the nine non-H atoms of the pyrrolopyridazine moiety is 0.016(3) Å (for atom C16). This system is practically coplanar with the chlorophenyl residue (dihedral angle between LS planes 2.4(1)º). ellipsoids drawn at the 50% probability level [12] and (right) π-π stacking in the crystal Salient geometrical parameters for the heterocyclic system were compared with those in 1 [2]. While both crystal structures were determined from low temperature intensity data (113 K for 4, 100 K for 1), it is noteworthy that the standard deviations in bond lengths for 4 (0.003-0.004 Å) are an order of magnitude smaller than those reported for 1 (0.037 Å [2]), justifying our reported analysis and allowing a more precise description of this heterocyclic system. The N-N bond length in 4 is 1.359(3) Å and the length C8-N9 is 1.314(3) Å. Given the relative standard deviations, these values overlap those quoted for 1 [2]. The carbon-carbon bonds in the 5-membered ring of 4 nominally span a narrower range (1.378(4)-1.396(5) Å) than that observed in 1 (1.383-1.426 Å). This is attributed to very significant electronic effects operating in 1 owing to the presence of two methyl ester substituents (Scheme 1). The asymmetry of the pyridazine ring of 4 is evident in Figure 1. In particular, the endocyclic angles subtended at N9 and C11 are equal (115.8(2), 115.7(3)º respectively) and significantly smaller than that subtended at N10 (126.1(2)º). Ring conjugation is reflected in the C5-C8 length of 1.490(4) Å, typical of e.g. biphenyls.
The likelihood of graphitic-type π-π stacking of these aromatic molecules in the crystal (Figure 1, right) was originally inferred from observation of the very short unit cell a-axis of 3.8568(1) Å. Molecules of 4 stack by translation along the x-direction forming columns. Crystal packing viewed parallel to the stacking direction is shown in Figure 2. Because of their steep inclinations to the bc-face of the unit cell, molecules of 4 stack in an offset face-to-face mode (Figure 2, right) with an interplanar separation of 3.400 Å (i.e. significantly < a). This distance matches those reported in crystals of 1 and related heterocyclic aromatic systems (range 3.31-3.39 Å), for which it has been suggested that the strength of π stacking is sufficient for applications requiring high electron mobility [2]. The stacking offset in 4 results in the shortest centroid⋅⋅⋅centroid distance (3.635 Å) being that between the pyridazine ring of a molecule at x, y, z and the pyrrole ring of the translated molecule at 1+x, y, z. The presence of only weak π-π stacking interactions in crystals of 4 is consistent with its low melting point of 54-55ºC. The X-ray analysis thus shows conclusively that the preparation and crystallization of 4 have achieved the desired goal in the solid state, namely extension of the π-electron system of the pyrrolo[1,2-b]pyridazine.

General
Melting points were determined on a Boëtius hot plate and are uncorrected. The NMR spectra were recorded on a Varian Gemini 300 BB instrument, operating at 300 MHz for 1 H and 75 MHz for 13 C. IR spectra were recorded with a UR-20 Carl Zeiss-Jena spectrometer.

X-ray analysis of 4
A small fragment was cut from a needle of 4 and mounted on a Nonius Kappa CCD four-circle diffractometer. Intensity data were collected using Mo-Kα radiation (λ = 0.71069 Å) with the crystal cooled in a stream of N 2 from a Cryostream cooler (Oxford Cryosystems, UK). The data-collection strategy (program COLLECT [13]) involved suitable combinations of 1.0° ϕand 0.60º ω-scans. Program DENZO-SMN [14] was used for cell refinement (15365 reflections in the θ-range 0.21-27.48°) and data reduction. The SADABS program [15] was used to apply absorption corrections. The structure was solved with the SHELXS86 program [16] and refined on F 2 with SHELXL97 [17], all non-hydrogen atoms being modelled anisotropically. All H atoms were located in difference electrondensity maps and were included in idealized positions in a riding model with isotropic thermal parameters equal to 1.2 times those of their parent atoms. In the final cycles of refinement, leastsquares weights of the form w = 1/[σ 2 (F o ) 2 + (aP) 2