ANALYTICAL SCIENCES 2008, VOL.

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X-ray Structure Analysis Online

X-ray Structure of a 3,4-Dihydropyrrolo[1,2-b]pyridazine Derivative

Mino R. CAIRA,* Florea DUMITRASCU,** Marcel M. POPA**
*Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa **Centre of Organic Chemistry C. D. Nenitzescu, Romanian Academy, Spl. Independentei 202B, Bucharest 060023, Romania

The X-ray structure of the compound dimethyl 2,7-dimethyl-pyrrolo[1,2-b]pyridazine-5,6-dicarboxylate was determined to establish the molecular geometry and conformation of its novel 6,5-bicyclic system. The compound crystallizes in the space group P21/n with a = 7.9910(2), b = 13.4005(3), c = 11.7950(3), b = 90.213(1), and Z = 4. A puckering analysis indicated a screw-boat conformation for the six-membered ring with the torsion angle C2C3C4C5 having a magnitude of 34.5(2). (Received May 19, 2008; Accepted June 30, 2008; Published on web August 19, 2008)

The stereochemical features of several cycloadducts obtained by the reaction of heteroaromatic N-ylides with olefinic and acetylenic dipolarophiles, as well as those of their intermediates and chemical transformation reaction products, were determined by single crystal X-ray analysis during the last three years.14 In a recent report on a novel synthesis of highly fluorescent pyrrolo[1,2-b]pyridazines,1 we gave an account of the selective reduction of these molecules that leads to isolation of the corresponding 3,4-dihydro derivatives, of which compound 1 (Fig. 1) is an example. Little information is available concerning the conformational preferences of the novel 6,5-bicyclic system found in 1. In order to establish the influence of the substituents on the conformation of this type of dihydro derivative, the structure of compound 1 (Fig. 1) was therefore determined for a comparison with that of an analogue (here referred to as 2) in which the substituent on C2 is a phenyl group, while a methyl group is lacking at C7.1 Compound 1, obtained by a reduction of the parent pyrrolo[1,2-b]pyridazine with Zn in AcOH under reflux,1 was recrystallized from a solution of dichloromethane and ethanol. This afforded colorless crystals (m.p. 99 101C). X-ray data were collected from a crystal of size 0.10 0.15 0.17 mm on a Nonius Kappa CCD diffractometer with the crystal cooled to 113(2)K. Laue symmetry 2/m indicated the monoclinic system;

the space group P21/n (alternative setting of space group P21/c, no. 14) was deduced from systematic absences. Lp-corrections were applied and the structure was solved by direct methods and refined by full-matrix least squares on F2. All hydrogen atoms were located in difference Fourier maps, and were subsequently added at idealized positions in a riding model with Uiso set at 1.2 1.5-times those of their parent atoms. All non-H atoms were refined anisotropically. Crystal data and refinement details are listed in Table 1. Final atomic co-ordinates and equivalent thermal parameters appear in Table 2. An inspection of the bond lengths (Table 3) for the bicyclic system shows that they are completely consistent with the formal bond orders indicated in Fig. 1. Their range is 1.284(2) 1.494(2), the bond N1C2 (formally double) being the shortest, while C4C5 (formally single) is the longest. The maximum deviation of any atom from the planar pyrrole ring is
Table 1 Crystal and experimental data 687794 C13H16N2O4 264.28 monoclinic P21/n 4 7.9910(2) 13.4005(3) 11.7950(3) 90.213(1) 1263.04(5)3 1.390 g cm3 3004 55.7 with Mo Ka 0.0451 <0.001 0.51 e3 0.35 e3 Nonius Kappa CCD DENZO-SMN SHELXS-97 full-matrix: SHELXL-97

Fig. 1

Chemical structure of compound 1.

To whom correspondence should be addressed. E-mail: Mino.Caira@uct.ac.za

CCDC deposition number Formula Formula weight Crystal system Space group Z a b c b V Dx No. of re ections used 2qmax R (2127 data, I > 2s(I)) (D/s)max nal cycle (Dr)max (Dr)min Measurement Program system Structure Determination Re nement

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Table 2 Atomic parameters (2) Atom x coordinates y and equivalent z thermal Ueq

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Ueq = (1/3)SiSjUij(ai*aj*)(aiaj). Table 3 Selected bond distances (), angles () and torsion angles ()

Fig. 2 ORTEP diagram of 1 with thermal ellipsoids drawn at the 50% probability level.

that of N6, 0.002(1). Of particular interest is the conformation of the 6-membered ring. A puckering analysis indicated that this is very similar to a screw-boat form with a puckering amplitude of 0.298(2). The six endocyclic torsion angles defining the precise conformation are listed in Table 3. As expected, the largest of these (C2C3C4C5, 34.5(2)) is that around the bond associated with the reduced centers C3, C4. The observed conformation of the 6-membered ring in 1 is very similar indeed to that in compound 2. All torsion angles in 1 are smaller in magnitude than those in 2, but the difference in any pair of corresponding torsion angles is less than 4. Thus, the substitution of a methyl group at C2 by a phenyl group has little effect on the ring conformation. A Cambridge Crystallographic Database search for the bicyclic ring system in 1 yielded only one hit, namely that in 3,4-dihydro-2,4,4,5,7-pentamethylpyrrolo[1,2-b]pyridazine (3),5 where the 6-membered ring differs from that in 1 by replacing the methylene hydrogen atoms at C4 by methyl groups. The 6membered ring in 3 adopts the same type of conformation as that in 1, but the extent of the ring deformation is much greater in 3 due to the steric bulk of the 4,4-dimethyl substituents (for example, in the molecule of 3, the torsion angle equivalent to C2C3C4C5 cited above is 45.2(2)). As indicated by the CCCO torsion angles (Table 3) and Fig. 2, one of the carbomethoxy groups in 1 is co-planar with the pyrrole ring, while the other is rotated out of the plane. Crystal stabilization in 1 is provided by van der Waals interactions as well as p-stacking. The latter (Fig. 3) involves

Fig. 3 Stacking of molecules along the x-direction in the crystal. The dotted lines indicate p-interactions.

the pyrrole rings of centrosymmetrically-related molecules with a centroidcentroid distance of 3.602(1). Pairs of molecules related in this way stack in columns parallel to the crystal aaxis.

Acknowledgements
MRC thanks the University of Cape Town and the National Research Foundation for research support.

References
1. F. Dumitrascu, M. R. Caira, B. Draghici, M. T. Caproiu, and D. G. Dumitrescu, Synlett., 2008, 813. 2. F. Dumitrascu, M. R. Caira, L. Barbu, B. Miu, and B. Draghici, Anal. Sci., 2008, 24, x27. 3. F. Dumitrascu, M. R. Caira, C. Draghici, and D. Dumitrescu, Anal. Sci., 2006, 22, x259. 4. F. Dumitrascu, M. R. Caira, C. Draghici, and M. T. Caproiu, Anal. Sci., 2007, 23, x13. 5. D. E. Jackman, A. W. Burgstahler, B. Lee, and R. I. Sheldon, Cryst. Struct. Commun., 1982, 11, 1111.