Buthalital and methitural – 5,5-substituted derivatives of 2-thiobarbituric acid forming the same type of hydrogen-bonded chain

In the title structures, each molecules is connected to two other molecules via four N—H⋯O hydrogen bonds, resulting in a chain with a sequence of (8) rings.


Chemical context
Buthalital (I) and methitural (II) are 5,5-disubstituted derivatives of 2-thiobarbituric acid. Compounds of the thiobarbiturate class differ from the corresponding barbiturates in that the ketone group at the 2-position is replaced by a thione group. Thiobarbiturates are used as injection narcotics for the induction of general anaesthesia or to produce complete anaesthesia of short duration. The sodium salt of (I) was originally developed as a short-acting anaesthetic but was found to have an extremely rapid elimination rate. Similarly, (II) was marketed in the 1950s as an ultra-short-acting intravenous anaesthetic.

Supramolecular features
The crystal structure of (I) contains N1-H1Á Á ÁO4 i and N3-H3Á Á ÁO6 ii bonds (Fig. 3, Table 1). Each molecule is linked to two neighbouring molecules via two-point connections and R 2 2 (8) rings (Etter et al. 1990, Bernstein et al., 1995. The resulting chain structure (topological type 2C1) contains a twofold screw axis and runs parallel to the b axis. The mean planes of neighbouring pyrimidine rings in the chain form an angle of approximately 40 with one another. The chain structure of (I) belongs to the C-2 type, which also occurs in a number of 5,5-disubstituted barbituric acid derivatives (Gelbrich et al., 2016a). The four shortest intermolecular contacts of the sulfur atom (SÁ Á ÁH distances between 2.97 and 3.01 Å ; close to the sum of van der Waals radii) involve both CH 2 groups of a neighbouring molecule and one CH 3 group belonging to the isobutyl substituent of two other molecules.

Figure 1
The molecular structure of (I), with displacement ellipsoids drawn at the 50% probability level and H atoms drawn as spheres of arbitrary size.
neighbouring molecules so that a C-2 chain structure is formed that propagates parallel to the c axis. In this case, the C-2 chain contains two crystallographically distinct R 2 2 (8) rings which are centred either by a twofold axis or an inversion centre (Fig. 4, Table 2). The mean planes of adjacent pyrimidine rings in the same chain are either coplanar with one another (if the corresponding molecules are related by an inversion operation), or they form an angle of 75 (if the molecules are related by a 180 rotation). The sulfur atom S9 of the 2-(methylthio)ethyl substituent forms an intermolecular contact (SÁ Á ÁH = 2.86 Å ) with the sec-butyl group of a molecule belonging to a neighbouring chain and S2 lies in close proximity to the methyl group of a 2-(methylthio)ethyl substituent (SÁ Á ÁH = 2.96 Å ).

Figure 3
The C-2-type bonded chain of (I). O and H atoms directly involved in N-HÁ Á ÁO interactions are drawn as balls and H atoms bonded to C atoms are omitted for clarity. The chain displays a twofold screw symmetry and contains just one type of R 2 2 (8) ring. [Symmetry codes: (i) Àx + 1 2 , y + 1 2 , Àz + 3 2 ; (ii) Àx + 1 2 , y À 1 2 , Àz + 3 2 .]  as well as N-HÁ Á ÁS bonds, with the latter interaction resulting in R 2 2 (8) rings. Numerous 5,5-substituted derivatives of barbituric acid are known to form N-HÁ Á ÁO=C-bonded chains exhibiting the 2C1 topology, with their molecules being linked by two-point connections resulting in the formation of characteristic R 2 2 (8) rings. Chains exhibiting these specific properties can be classified into two distinct types, denoted as C-1 and C-2 (Gelbrich et al., 2016a;see Fig. 5). The less frequent of these two types, C-2, is also the chain motif of (I) and (II). It is characterized by the employment of each of the topologically equivalent C4 and C6 carbonyl groups, but not the C2 group, as a hydrogenbond acceptor.

Synthesis and crystallization
Single crystals of (I) were produced by sublimation between two glass slides separated by a spacer ring (height: 1 cm), using a hot bench at a temperature of 403 K. As confirmed by PXRD, the phase investigated by us is identical with that of the original sample from the1940s obtained from our archive. The melting point of this phase of 422 K was determined with hot-stage microscopy. Heating the quench-cooled melt of (I) above 323 K resulted in the crystallization of a second form. Isolated, individual crystals of this second form melted at approximately 387 K. In other experiments, a phase transition from the low-melting form II to a high-melting form I occurred on heating, usually between 378 and 383 K (see Supporting information). These observations are consistent with a previous description by Brandstä tter- Kuhnert & Aepkers (1962).
The crystals of (II) investigated in this study were taken from a sample obtained from Merck AG, Darmstadt, Germany. These crystals melted within a relatively broad temperature range between 361 and 366 K.

Refinement
Refinement on F 2 Least-squares matrix: full R[F 2 > 2σ(F 2 )] = 0.038 wR(F 2 ) = 0.084 S = 1.14 2813 reflections 192 parameters 2 restraints Hydrogen site location: mixed H atoms treated by a mixture of independent and constrained refinement w = 1/[σ 2 (F o 2 ) + (0.0192P) 2 + 6.3729P] where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.53 e Å −3 Δρ min = −0.29 e Å −3 Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Geometric parameters (Å, º)