Received 11 August 2004
Hydrogen-bonded chains in 5-methyl-2-trifluoromethyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one and hydrogen-bonded chains of rings in 5-amino-3-trifluoromethyl-1H-1,2,4-triazole-5-methyl-2-trifluoromethyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (1/1), the co-crystal of a reaction product and one of its precursors
Nubia Boechat,a Karen D. B. Dutra,a Alessandra L. Valverde,a Solange M. S. V. Wardell,a John N. Lowb+ and Christopher Glidewellc*
aFundação Oswaldo Cruz, Far Manguinhos, Rua Sizenando Nabuco, 100 Manguinhos, 21041250 Rio de Janeiro, RJ, Brazil,bDepartment of Chemistry, University of Aberdeen, Meston Walk, Old Aberdeen AB24 3UE, Scotland, and cSchool of Chemistry, University of St Andrews, Fife KY16 9ST, Scotland
In the title compounds, C7H5F3N4O, (I), and C3H3F3N4·C7H5F3N4O, (II), all of the molecular components exhibit some polarization of their molecular-electronic structures. The molecules in (I) are linked into simple C(6) chains, while in (II), the components are linked by a combination of two-centre N-HN and N-HO, and three-centre N-H(O,N) hydrogen bonds into chains containing R(5), R(6) and R(8) rings.
In the course of our studies of fluorinated triazole precursors of potential antimalarial compounds, we needed to prepare 3-methyl-5-(trifluoromethyl)-1,2,4-triazolo[1,5-a]pyrimidin-7-one, (I). The preparation of this compound by the reaction of 5-amino-3-trifluoromethyl-1H-1,2,4-triazole with ethyl acetoacetate has recently been reported (Zohdi, 1997), and use of the reported chromatographic purification readily affords pure (I). However, we have found that, when purification of the crude reaction product is attempted using recrystallization methods, the crystalline material obtained is not the expected triazolopyrimidinone, (I), but a co-crystal, (II), containing a 1:1 molar ratio of (I) with the starting triazole. We report here the molecular and supramolecular structures of both (I) and the co-crystal, (II).
In both (I) and (II) (Figs. 1 and 2), the bond lengths in the six-membered rings (Tables 1 and 3) indicate that the O14-C14-C15-C16-N17 fragment constitutes a vinylogous amide, with a significant contribution from the polarized form, (Ia). The other bond distances and angles in (I) show no unexpected values. In particular, the five-membered ring of the bicyclic component shows very strong bond fixation with a clear distinction between single and double bonds.
Within the triazole component of (II), the N21-C25 and N25-C25 bonds are too similar in length to be convincingly represented as double and single bonds, respectively. In pure 5-amino-3-trifluoromethyl-1H-1,2,4-triazole itself, (III) (Borbulevych et al., 1998), the corresponding bonds differ in length by only 0.022 (2) Å. The other C-N bond lengths within this ring are typical of their types (Allen et al., 1987) in both (II) and (III), and the dimensions thus suggest that there is some contribution from the polarized form, (IIIa), in both (II) and (III).
The molecules of (I) are linked into C(6) chains (Bernstein et al., 1995) by a single, almost linear, N-HO hydrogen bond (Table 2). Amine atom N7 in the molecule at (x, y, z) acts as donor to carbonyl atom O4 in the molecule at (x - 1, - y, z - ), so forming a chain running parallel to the  direction and generated by the c-glide plane at y = (Fig. 3). Two such chains, which are related to one another by inversion and hence antiparallel to each other, pass through each unit cell, but there are no direction-specific interactions between adjacent chains.
Within the asymmetric unit of compound (II), the independent molecular components are linked by two nearly linear N-HN hydrogen bonds (Table 4), forming an R(8) motif. These units are linked into a chain by one two-centre N-HO hydrogen bond and one three-centre N-H(O,N) hydrogen bond. Atom N25 at (x, y, z) acts as hydrogen-bond donor, via atom H25B, to atom N11 at (x - , - y, + z). At the same time, atom N24 at (x, y, z) acts as donor to both atoms O14 and N13 at (x - , - y, + z), forming a markedly asymmetric, but planar, three-centre interaction. Propagation of these hydrogen bonds then forms a complex chain of rings, containing [R(5)][R(6)][R(8)] sequences of three edge-fused rings (Fig. 4). This chain is generated by the c-glide plane at y = and runs parallel to the  direction. Two chains of this type pass through each unit cell, but there are no direction-specific interactions between adjacent chains.
It is pertinent to reconsider the supramolecular structure of the pure triazole component, (III). This was described (Borbulevych et al., 1998) as forming hydrogen-bonded layers parallel to the ab plane. However, analysis of the original atom coordinates using PLATON (Spek, 2003) clearly shows that the supramolecular structure consists of a C(4)C(5)[R(7)] chain of rings running parallel to the  direction (Fig. 5). The formation of this chain utilizes only two of the three available N-H bonds, but there are no plausible acceptors available within hydrogen-bonding range of the third N-H bond, so that the supramolecular structure of (III) is properly described as one-dimensional.
| || Figure 1 |
The molecule of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
| || Figure 2 |
The independent molecular components of (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
| || Figure 3 |
Part of the crystal structure of (I), showing the formation of a chain along . For the sake of clarity, H atoms bonded to C atoms have been omitted. Atoms marked with an asterisk (*) or a hash (#) are at the symmetry positions (x - 1, - y, z - ) and (1 + x, - y, + z), respectively.
| || Figure 4 |
Part of the crystal structure of (II), showing the formation of a chain of rings along . For the sake of clarity, H atoms bonded to C atoms have been omitted. Atoms marked with an asterisk (*) or a hash (#) are at the symmetry positions (x - , - y, + z) and ( + x, - y, z - ), respectively.
| || Figure 5 |
Part of the crystal structure of (III) (Borbulevych et al., 1998), showing the formation of a chain of rings along . The original atomic coordinates and atom-labelling scheme have been used. Atoms marked with an asterisk (*), a hash (#) or a dollar sign ($) are at the symmetry positions (-x, + y, - z), (x, 1 + y, z) and (-x, y - , - z), respectively.
For the preparation of (I) and (II), an equimolar mixture of 3-amino-5-trifluoromethyl-1,2,4-triazole and ethyl acetoacetate (1 mmol of each) in toluene (27 ml) was heated under reflux for 2 h. The mixture was cooled to ambient temperature and the resulting solid was collected. Chromatographic purification (Zohdi, 1997) gave pure (I), and crystals of (I) suitable for single-crystal X-ray diffraction were grown from a solution in ethanol. By contrast, successive recrystallizations of the crude reaction mixture from EtOH and then from Me2CO-CHCl3 (1:1 v/v) gave crystals of (II) suitable for single-crystal X-ray diffraction.
For compound (I), the space group P21/c was uniquely assigned from the systematic absences. Crystals of (II) are monoclinic and the systematic absences permitted Cc and C2/c as possible space groups. Consideration of the unit-cell volume suggested space group Cc, and this was confirmed by the subsequent structure analysis. All H atoms were located from difference maps and then treated as riding atoms, with C-H distances of 0.95 (ring CH) or 0.98 Å (CH3) and N-H distances of 0.88 Å, and with Uiso(H) = 1.2Ueq(C,N), or 1.5Ueq(C) for the methyl group. In the absence of any significant anomalous scattering, the Flack (1983) parameter was indeterminate (Flack & Bernardinelli, 2000) and it was not possible to establish the correct orientation of the structure of (II) relative to the polar-axis directions (Jones, 1986). Accordingly, the Friedel-equivalent reflections were merged prior to the final refinements. However, although the data are 99.2% complete to = 27.47°, with merged equivalents the ratio of data to parameters is rather low at only 7.0.
For both compounds, data collection: KappaCCD Server Software (Nonius, 1997); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN. For compound (I), program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997). For compound (II), program(s) used to solve structure: OSCAIL (McArdle, 2003) and SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: OSCAIL and SHELXL97 (Sheldrick, 1997). For both compounds, molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 and PRPKAPPA (Ferguson, 1999).
Supplementary data for this paper are available from the IUCr electronic archives (Reference: SK1761 ). Services for accessing these data are described at the back of the journal.
The X-ray data were collected at the EPSRC X-ray Crystallographic Service, University of Southampton, England; the authors thank the staff for all their help and advice. JNL thanks NCR Self-Service, Dundee, for grants which have provided computing facilities for this work. NB, KDBD and SMSVW thank CNPq for financial support.
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1-19.
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.
Blessing, R. H. (1995). Acta Cryst. A51, 33-37.
Blessing, R. H. (1997). J. Appl. Cryst. 30, 421-426.
Borbulevych, O. Y., Shishkin, O. V., Desenko, S. M., Chernenko, V. N. & Orlov, V. D. (1998). Acta Cryst. C54, 442-444.
Ferguson, G. (1999). PRPKAPPA. University of Guelph, Canada.
Flack, H. D. (1983). Acta Cryst. A39, 876-881.
Flack, H. D. & Bernardinelli, G. (2000). J. Appl. Cryst. 33, 1143-1148.
Jones, P. G. (1986). Acta Cryst. A42, 57.
McArdle, P. (2003). OSCAIL for Windows. Version 10. Crystallography Centre, Chemistry Department, NUI Galway, Ireland.
Nonius (1997). KappaCCD Server Software. Windows 3.11 Version. Nonius BV, Delft, The Netherlands.
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.
Spek, A. L. (2003). J. Appl. Cryst. 36, 7-13.
Zohdi, H. F. (1997). J. Chem. Res. (S), pp. 392-393; (M), pp. 2378-2394.