Structures of the adducts urea:pyrazine (1:1), thiourea:pyrazine (2:1) and thiourea:piperazine (2:1)

1 Introduction

Urea and thiourea have a marked tendency to form hydrogen-bonded adducts with other simple organic compounds. If the latter are liquids at room temperature, the adducts can be described as solvates. It is logical to assume that the chances of forming an adduct are maximized if the concentration of the partner is as high as possible, and using liquids as partners is thus a sensible strategy.

There are three easily recognisable types of urea adduct. First, in some 1:1 complexes [1], urea molecules are connected to form chains of rings with graph set C(4)[R21(6)]; the solvent molecules connect adjacent urea chains. Secondly, 1:1 complexes with aza-aromatics such as 2-picoline [2] or 2,6-lutidine [3], [4] (but also with N,N-dimethylacetamide [5]) contain urea ribbons, consisting of linked R22(8) rings; the solvent molecules are attached terminally to the ribbons. Thirdly, 2:1 complexes are formed with other aza-aromatics [4], whereby the urea residues form corrugated layers in which the ribbons are connected laterally, and from which some urea NH groups project outwards and are hydrogen-bonded to the aza-aromatics. For a slightly more detailed overview, see our recent paper [6]. A general review of urea adducts has been presented by Custelcean [7].

Thiourea adducts tend to display more complex packing patterns than urea adducts; this is because the urea C=O group predominantly accepts hydrogen bonds from donors within or close to its sp² plane, whereas the thiourea C=S group can accept hydrogen bonds from donors way outside the corresponding plane [8], [9], [10]. However, some of the above-mentioned motifs for urea can often be recognized as substructures, e.g. in the ternary adduct thiourea: 2,5-dimethylpyrazine : methanol (1:1:1) [11].

We recently investigated adducts of urea with various methyl-substituted pyrazines [6]. Although most of the pyrazine derivatives were liquids, we also succeeded in obtaining a 2:1 adduct of urea and 2,6-dimethylpyrazine, a solid, from a solution in ethanol. This prompted us to employ unsubstituted pyrazine and piperazine, also solids at room temperature, in similar investigations. Here we present the structures of the adducts urea:pyrazine (1:1) (1), thiourea:pyrazine (2:1) (2), and thiourea:piperazine (2:1) (3).

2 Results and discussion

The structure determination of the 1:1 urea:pyrazine adduct 1 (Figs. 1 and 2 ) shows that it is closely related to the 1:1 dioxane adduct [1], although it is not isotypic to any previously known urea adduct. The compound crystallizes in space group P2/c, whereby the C=O group of the urea lies along a two-fold axis and the pyrazine molecule lies across an inversion centre. The C(4)[R21(6)] urea chains run parallel to the b axis and are crosslinked by the pyrazine molecules via hydrogen bonds of the form N–H···N. The layer structure is parallel to (102). Neighbouring layers are linked by the marginal contact H12···O1 (−1+x, y, z) 2.65 Å.

Fig. 1:

The structure of compound 1 in the crystal. Ellipsoids represent 50% probability levels. Only the asymmetric unit is labelled. The dashed line represents a hydrogen bond.

Fig. 2:

Packing diagram of compound 1 viewed perpendicular to the plane (102). Dashed lines represent hydrogen bonds.

The 2:1 thiourea:pyrazine adduct 2 (Fig. 3) crystallizes in space group Fddd. The asymmetric unit consists of a thiourea molecule with the C=S group lying along the two-fold axis ⅛, ⅛, z; the pyrazine nitrogen atom also lies on this axis, whereby the pyrazine molecule is centred on the special position ⅛, ⅛, ⅛ and thus displays crystallographic 222 symmetry. A view of the packing perpendicular to (1̅10) (Fig. 4) reveals an apparently simple picture of the well-known R22(8) ribbon structure, here parallel to [110], for the thiourea molecules; the pyrazine residues are attached to the remaining thiourea NH groups via bifurcated hydrogen bonds (N–H···)₂S. For most such structures, however, the aza-aromatic rings occupy terminal positions on the ribbons. Here, the crystallographic symmetry of the pyrazine molecules means that the other ends of these molecules are also attached to thiourea ribbons, but now parallel to [1̅10] and thus perpendicular to the first set of ribbons, forming a crosslinked three-dimensional structure. This also leads to short S···S contacts (operator ¼–x, y, 1¼–z; recognizable but not explicitly drawn in Fig. 4) of 3.3335(5) Å between ribbons. To maintain contacts between both thiourea chains, the pyrazine ring should adopt an ideal interplanar angle of 45° to both; in fact this angle is 43.7°.

Fig. 3:

The structure of compound 2 in the crystal. Only the asymmetric unit is labelled. Ellipsoids represent 50% probability levels. Dashed lines represent hydrogen bonds.

Fig. 4:

Packing diagram of compound 2 viewed perpendicular to (1̅10). Dashed lines represent hydrogen bonds.

The 2:1 thiourea:piperazine adduct 3 (Fig. 5) crystallizes in space group C2/c. The thiourea molecule occupies a general position, whereas the piperazine lies across an inversion centre. The packing can be interpreted in terms of thiourea layer structures (Fig. 6) parallel to the ab plane in the regions z≈¼, ¾. The contact H01···S1 is rather long and not very linear (2.91 Å, 131°), and the system could alternatively be described as a three-centre interaction including the even longer contact H01···S1 (1½–x, ½+y, ½–z; 3.11 Å, 143°). Between the thiourea layers, the piperazines occupy the regions at z≈0, ½ and are linked to the thioureas by two hydrogen bonds at each piperazine nitrogen atom N11 (the N11–H05 donor function occupies the equatorial position at piperazine) (Fig. 7). An additional contact C12–H12A···S1 (−½+x, ½+y, z; 2.82 Å, 152°) is not shown in Fig. 7.

Fig. 5:

The structure of compound 3 in the crystal. Only the asymmetric unit is labelled. Ellipsoids represent 50% probability levels. The dashed line represents a hydrogen bond.

Fig. 6:

Packing diagram of compound 3; thiourea substructure viewed perpendicular to the ab plane in the region z≈¼. Dashed lines represent hydrogen bonds.

Fig. 7:

Packing diagram of compound 3 viewed perpendicular to the bc plane; piperazine layers alternating with thiourea layers. Dashed lines represent hydrogen bonds. Methylene hydrogen atoms are omitted for clarity.

3 Preparation of the adducts

Adduct 1: 60 mg (1 mmol) urea and 800 mg (10 mmol) pyrazine were each dissolved in 2 mL methanol. The solutions were combined and overlayered with di-isopropyl ether. Colourless prisms of 1 formed overnight. Lower molar ratios than 10:1 led either to no crystals or to crystals of urea (identified by the cell constants). Elemental analyses were unsatisfactory, possibly because of contamination with urea.

Adduct 2: 76 mg (1 mmol) thiourea and 160 mg pyrazine (2 mmol) were each dissolved in 2 mL methanol. The solutions were combined and overlayered with di-isopropyl ether. Colourless blocks and tablets of 2 formed overnight. – Analysis: Found C 30.62, H 5.26, N 35.97, S 28.08%; calcd. for C₆H₁₂N₆S₂ (M=232.34) C 31.02, H 5.21, N 36.17, S 27.60%.

Adduct 3: 76 mg (1 mmol) thiourea and 172 mg piperazine (2 mmol) were each dissolved in 2 mL methanol. The solutions were combined and overlayered with di-isopropyl ether. Colourless blocks of 3 formed overnight. – Analysis: Found C 30.42, H 7.64, N 34.59, S 27.33%; calcd. for C₆H₁₈N₆S₂ (M=238.38) C 30.23, H 7.61, N 35.26, S 26.90%.

Yields were not recorded, because the intention was merely to establish the existence and the structure of new adducts. Attempts to prepare an adduct of urea and piperazine were unsuccessful; this might be attributable to the limited solubility of piperazine in methanol.

4 Crystal structure determinations

Crystal data are summarized in Table 1; hydrogen bonds are listed in Table 2. Crystals were mounted in inert oil on glass fibres and transferred to the cold gas stream of the diffractometer (Oxford Diffraction Xcalibur E, using monochromated Mo Kα radiation). Absorption corrections were applied on the basis of multi-scans; appropriate scaling was applied. Structures were refined anisotropically on F² using the program Shelxl-97 [12], [13]. NH hydrogen atoms were refined freely, methyl groups as idealized rigid groups allowed to rotate but not tip, other hydrogen atoms using a riding model starting from calculated positions.

For NH₂ groups, the NH hydrogen atoms cis to O=C or S=C across the corresponding N–C bond are numbered even and the trans NH hydrogen atoms odd.

CCDC 1537861 (1), 1537862 (2), and 1537863 (3) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre viawww.ccdc.cam.ac.uk/data_request/cif.