Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

Summary The three possible structural isomers of 4-(pyridyl)pyrimidine were employed for the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3-dipolar cycloaddition reaction of their corresponding N-ylides generated in situ from their corresponding cycloimmonium bromides. In the case of 4-(3-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine the quaternization reactions occur as expected at the pyridine nitrogen atom leading to pyridinium bromides and consequently to new indolizines via the corresponding pyridinium N-ylides. However, in the case of 4-(2-pyridyl)pyrimidine the steric hindrance directs the reaction to the pyrimidinium N-ylides and, subsequently, to the formation of the pyrrolo[1,2-c]pyrimidines. The new pyrrolo[1,2-c]pyrimidines and the new indolizines were structurally characterized through NMR spectroscopy. The X-ray structures of two of the starting materials, 4-(2-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine, are also reported.


General
Melting points were measured using a Bőetius hot plate microscope and are uncorrected. 1 H NMR and 13 C NMR spectra were recorded on a Varian Gemini 300BB operating at 300 MHz for 1 H and 75 MHz for 13 C. The spectra were recorded in CDCl 3 and DMSO at 298K and the chemical shifts are relative to TMS used as the internal standard. The bidimensional correlation spectra (COSY, HETCOR) were performed for complete assignment of chemical shifts. Fourier-transform IR spectra were recorded on a Bruker Vertex 70 spectrometer with horizontal device for attenuated reflectance and diamond crystal, on a spectral window ranging from 4000 to 400 cm −1 or on a Nicolet Impact Spectrometer 410 in KBr pellets. Elemental analysis was performed on a Perkin Elmer CHNS/O Analyser Series II 2400 apparatus and the results were in agreement with the calculated values. All starting materials and solvents were purchased from common commercial suppliers and were used without purification unless otherwise noted.

Experimental:
All experimental conditions and diffractometer details are listed in the CIF files that accompany the submission. These files also list all relevant crystallographic data S3 (atomic co-ordinates, thermal displacement parameters, bond lengths and angles, and torsion angles) as well as software employed in data-collection, data-processing, structural solutions and refinements. The strategy for refining the disordered structures is described below.

Details of structural modelling
As explained in the manuscript, since the molecules of compound 6 (Z = 2 molecules per unit cell) and compound 8 (Z = 1) are not centrosymmetric, but are required to be located on centres of inversion in their respective space groups (monoclinic, P2 1 /n and triclinic, P(-1)), it was necessary to postulate (planar) centrosymmetric molecular models.
The initial structure solutions by direct methods yielded the expected hexagonal asymmetric unit (symbolic co-ordinates x, y, z) in each case, to which the second S4 hexagon (at -x, -y, -z) of each molecule could be added by applying the centre of inversion.
Compound 6: The two planar rotamers (6a, 6b) are shown in Figure S1, together with the results of adding a centre of inversion '(-1)' to each. Thus, if the rotamer 6a were to crystallize as such, the requirement of centrosymmetry would result in model A, with the N atoms at positions 2, 4 and 6, each having a site-occupancy factor (s.o.f.) of 0.5 (and therefore each being coincident with carbon atoms, also having a s.o.f. of 0.5 each). If, instead, the rotamer 6b were to crystallize, model B would result in the crystal.
These models should be distinguishable most obviously from the pattern of H atoms appearing in difference Fourier syntheses. Specifically, for model A, atoms 2-6 should all

S5
have attached H atoms, those at positions associated with atoms 3 and 5 having full occupancy and those at positions associated with atoms 2, 4 and 6 only half occupancy. Instead, for model B the ring should contain no H atom attached to N at position 2, full H atoms associated with positions 3, 5 and 6, and a H atom with half occupancy associated with position 4.
During the refinement of the structure of 6 with isotropic thermal parameters, it was quite clear that the H atoms appeared at the expected positions corresponding to model B, at ~ 1Å away from the parent atoms with difference electron densities at the positions indicated having the values shown in parentheses: 2 (0.0 eÅ -3 ), 3 (0.60 eÅ -3 ), 4 (0.37 eÅ -3 ), 5 (0.72 eÅ -3 ), 6 (0.70 eÅ -3 Similar considerations were given to obtaining an appropriate centrosymmetric model for the molecule of 8. Figure S2  Following isotropic refinement, anisotropic thermal displacement parameters were introduced (with EADP maintained). All H atoms were placed in a riding model with U iso = 1.2U eq (parent atom).

Isostructurality of 6 and 4,4'-bipyrimidine
Reference is made to this instance of crystal isostructurality in the manuscript.
The crystallographic data for compound 6 and those for 4,4'-bipyrimidine ([1], refcode SACPAN in the Cambridge Structural Database) were used as input to the program Lazy Pulverix [2] to compute their powder X-ray diffraction patterns. These are shown as Figure S3 below, from which it is clear that the two phases are isostructural.