Bis ( cyclopropanecarbonyl ) amino ]-4 , 6-dichloro-pyrimidine containing a short cyclopropyl CÐH O interaction

A great deal of research has been carried out on pyrimidine systems, fuelled by their important biological applications and properties (Brown, 1994). Various dihaloaminopyridines and dihaloaminopyrimidines have proven to be useful in terms of their antiviral activity, particularly for their action towards the Herpes virus (Giovanninetti et al., 1980). As part of our general investigations in this area, the title compound, (I), C12H11Cl2N3O2, has been synthesized, albeit in moderate yield. Similarly low yields have also been observed by Giovanninetti et al. (1980) in acylation reactions of dichloroaminopyrimidines.

The title compound, C 12 H 11 Cl 2 N 3 O 2 , possesses normal intramolecular geometrical parameters. The crystal packing is in¯uenced by CÐHÁ Á ÁO and possible weak %±% stacking interactions.

Comment
A great deal of research has been carried out on pyrimidine systems, fuelled by their important biological applications and properties (Brown, 1994). Various dihaloaminopyridines and dihaloaminopyrimidines have proven to be useful in terms of their antiviral activity, particularly for their action towards the Herpes virus (Giovanninetti et al., 1980). As part of our general investigations in this area, the title compound, (I), C 12 H 11 Cl 2 N 3 O 2 , has been synthesized, albeit in moderate yield. Similarly low yields have also been observed by Giovanninetti et al. (1980) in acylation reactions of dichloroaminopyrimidines.
Compound (I) possesses normal intramolecular geometrical parameters (Table 1). The 4,6-dichloropyrimidine moiety (C1± C4/N1/N2/Cl1/Cl2) is close to being planar; for the non-H atoms, the r.m.s. deviation from the least-squares plane is 0.031 A Ê . Atom N3 is signi®cantly displaced from the mean plane by 0.204 (3) A Ê . The dihedral angle between the aromatic ring and the C5/N3/C9 group is 74.81 (10) . The major conformational difference in the cyclopropanecarbonyl`arms' of (I) concerns the amide carbonyl (C5 O1 and C9 O2) groups. The ®rst of these is close to being eclipsed with respect to the N3ÐC3 bond, whereas the second is almost anti with respect to the same pair of atoms (Table 1). The cyclopropyl rings [mean CÐC = 1.504 (3) A Ê ; mean CÐCÐC = 60.0 (2) ] are unexceptional.
As well as van der Waals forces, the crystal packing in (I) appears to be in¯uenced by CÐHÁ Á ÁO interactions ( Table 2). The ®rst of these bonds involves the atoms C1ÐH1Á Á ÁO1 ii (see Table 2 for symmetry code), i.e. the aromatic H atom and an amide carbonyl O-atom acceptor. These bonds help stabilize the [001] stacks of (I) and are generated by c-glide symmetry. The second, with a near-linear C7ÐH4Á Á ÁO2 i bond angle of 173 and a very short HÁ Á ÁO separation of 2.35 A Ê , involves a cyclopropyl H atom and the other amide carbonyl O atom as the acceptor species, the acceptor generated by inversion symmetry (Fig. 2), which results in dimers of (I). Allen et al. (1996) have shown that CÐHÁ Á ÁO hydrogen bonds from cyclopropyl methylene groups are enhanced because strain inherent in the C3 ring tends to increase the acidity of the CH moieties involved, although the example here appears to be a particularly strong bond.
In combination, these effects result (Fig. 3) in stacks of molecules of (I) propagating along [001]. The stacks are crosslinked along [010] by the proposed C7ÐH4Á Á ÁO2 i ( Table 2) bonds, whereas along [100] only van der Waals interactions hold the adjacent stacks together. In this direction, the N1Á Á ÁCl2 iv [symmetry code (iv) x À 1, y, z] contact of 3.252 (2) A Ê is slightly less than the van der Waals radius sum of 3.30 A Ê for these species (Spek, 2003).

Experimental
To prepare (I), 4,6-dichloro-5-aminopyrimidine (0.412 g, 2.512 mmol) was placed in a twin-necked¯ask and was stirred in dry dichloromethane (35 ml) under a nitrogen atmosphere. The reaction mixture was cooled to 273 K, whereupon Hu È nig's base (7.54 mmol, 1.30 ml) was added, and the reaction was stirred for approximately 10 min. Cyclopropane carbonyl chloride (7.54 mmol, 0.68 ml) was then added, and the reaction was warmed to room temperature and stirred for 24 h. The progress of the reaction was monitored using thin-layer chromatography (TLC, solvent dichloromethane), showing the product with an R F of 0.19 The reaction mixture was then washed with saturated brine (3 Â 20 ml) and dried with magnesium sulfate, and the solvent was removed at reduced pressure. The resultant organic liquor was puri®ed using¯ash chromatography (solvent 3:0.1 chloroform/methanol). Overlap of the starting material with the product required the use of a different solvent system (2:2:0.1 dichloromethane/hexane/methanol) to further purify the product (R F = 0.17). Vapour diffusion crystallization was used to obtain white crystals of (I); dichloromethane was used as the solvent and hexane was used as the precipitant. The yield obtained was 0.063 g (8. Dimerization of molecules of (I) via the C7ÐH4Á Á ÁO2 i bond (symmetry code as in Table 2), with 50% probability displacement ellipsoids; all H atoms, except H4, have been omitted for clarity.
All H atoms were placed in calculated positions (CÐH = 0.95± 1.00 A Ê ) and re®ned as riding on their carrier atoms, with U iso (H) = 1.2U eq (carrier atom).
We thank the EPSRC UK National Crystallography Service (University of Southampton) for the data collection.

Special details
Experimental. Melting points were determined using a Kofler hot-stage apparatus and are uncorrected. Infrared spectra were recorded using a Nicolet Avatar 320 F T-IR spectrometer, using KBr discs. NMR spectra were determined using a Varian Unity Inova spectrometer (400 MHz, 1 H and 100 MHz, 13 C) using deuterated (2H)-chloroform as solvent, with the presence of residual CHCl 3 , as the reference at 7.26 p.p.m., with J values in Hz). Flash chromatography was carried out using silica gel (230-400 mesh), TLC was performed on plates cut from 20x20 cm aluminium sheets, coated with Merck Kieselgel 60 silica with F254 indicator. Dry dichloromethane was distilled under argon, from calcium hydride prior to use. All glassware was pre-dried in the oven before use and cooled in an argon atmosphere. Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq C1 0.5414 (