Crystal structure of (E)-2-amino-4-methylsulfanyl-6-oxo-1-{[(thiophen-2-yl)methylidene]amino}-1,6-dihydropyrimidine-5-carbonitrile

In the title compound 1-thiophen-2-ylmethyleneaminopyrimidine derivative, the pyrimidine and thienyl rings are inclined to one another by 42.72 (5)°. In the crystal, molecules are linked by N–H⋯Nnitrile and N–H⋯O=C hydrogen bonds, forming chains parallel to the b axis.


Chemical context
Pyrimidines are well known for their biological activities as antimetabolic agents and have attracted much attention from the standpoint of pharmaceutical chemistry. Many drugs, such as 5-fluorouracil, containing a pyrimidine moiety have been developed and used as anticancer agents. It is difficult to find a general method for the introduction of specific substituents into the pyrimidine nucleus directly, and thus many synthetic methods have been developed for the construction of pyrimidine rings bearing potential functional groups (Elgemeie & Sood, 2001). As part of our program directed toward the preparation of potential antimetabolites (Elgemeie & Hussain, 1994), we have recently reported various successful approaches for the syntheses of purine and pyrimidine analogues (Elgemeie, 2003;Elgemeie et al., 2009). Derivatives of these ring systems are interesting as antimetabolic agents in biochemical reactions (Scala et al., 1997).
We report herein on the synthesis and crystal structure of a new 1-thiophen-2-ylmethyleneaminopyrimidine derivative, obtained by reaction of dimethyl N-cyanodithioiminocarbonate with 1-cyanoacetyl-4-thiophenemethylidene semi- ISSN 2056-9890 carbazide in dioxane containing KOH at room temperature. To the best of our knowledge, this is the first example of this approach to be reported for N-substituted aminopyrimidine derivatives. The X-ray structure determination was undertaken to establish the nature of the product unambiguously.

Structural commentary
The molecular structure of the title compound is shown in Fig. 1. The E conformation across the double bond N2 C10 is confirmed, with a bond length of 1.2879 (14) Å . Both ring systems are, as expected, planar (r.m.s. deviations are 0.017 Å for the pyrimidine and 0.001 Å for the thienyl ring). Atom N2 lies 0.189 (2) Å out of the pyrimidine plane; all other immediate substituent atoms lie effectively in the ring plane. Carbon atom C7 of the thiomethyl group is rotated slightly out of the ring plane, with torsion angle N3-C4-S1-C7 being À6.30 (10) . The inter-planar angle between the rings is 42.72 (5) ; the relative orientation is influenced by the torsion angles C6-N1-N2-C10 = À51.78 (13), N1-N2-C10-C11 = 174.68 (9) and N2-C10-C11-S12 = 5.22 (15) . The NH 2 group is planar; the nitrogen atom lies only 0.048 (9) Å out of the plane of its substituents. The intramolecular contact H041Á Á ÁN2 = 2.22 (2) Å may be construed as a hydrogen bond, although the angle at the H atom is necessarily narrow at 108.4 (14) ( Table 1).

Figure 2
Crystal packing diagram of the title compound, viewed perpendicular to (102). Classical hydrogen bonds are drawn as thick dashed lines and 'weak' hydrogen bonds as thin dashed lines (see Table 1).
with the amino and C O functions located as for the title compound.

Synthesis and crystallization
Dimethyl N-cyanodithioiminocarbonate (0.01 mol) was added to a stirred solution of 1-cyanoacetyl-4-thiophenemethylidenesemicarbazide (0.01 mol) in dry dioxane (50 ml), containing potassium hydroxide (0.01 mol), at room temperature. The solution was stirred overnight at room temperature, after which a colourless solid product was collected by filtration and crystallized from ethanol (m.p. 541-542 K), giving colourless block-like crystals.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The NH hydrogen atoms were located in a difference Fourier map and freely refined. The Cbound H atoms were included in calculated positions and treated as riding atoms: C-H = 0.95-0.98 Å with U iso (H) = 1.5U eq (C) for methyl H atoms and 1.2U eq (C) for other H atoms. The methyl group was refined as an idealized rigid group, allowed to rotate but not to tip.

References
Agilent (    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. NH H atoms were refined freely. The methyl was refined as an idealized rigid group allowed to rotate but not tip (AFIX 137). Other H atoms were included using a riding model starting from calculated positions.