Nitrofurantoin methanol monosolvate

The antibiotic nitrofurantoin {systematic name: (E)-1-[(5-nitro-2-furyl)methylideneamino]imidazolidine-2,4-dione} crystallizes as a methanol monosolvate, C8H6N4O5·CH4O. The nitrofurantoin molecule adopts a nearly planar conformation (r.m.s. deviation = 0.0344 Å). Hydrogen bonds involve the co-operative N—H⋯O—H⋯O heterosynthons between the cyclic imide of nitrofurantoin and methanol O—H groups. There are also C—H⋯O hydrogen bonds involving the nitrofurantoin molecules which support the key hydrogen-bonding synthon. The overall crystal packing is further assisted by weak C—H⋯O interactions, giving a herringbone pattern.

There are also C-HÁ Á ÁO hydrogen bonds involving the nitrofurantoin molecules which support the key hydrogenbonding synthon. The overall crystal packing is further assisted by weak C-HÁ Á ÁO interactions, giving a herringbone pattern.

Comment
Polymorphism is an ability of a molecule to exist in two or more crystal structures. Incorporation of solvent molecules into the crystalline lattice are routinely referred to as solvates, inclusion complexes and/or pseudopolymorphs (Bernstein, 2002;Byrn et al., 1999;Aitipamula et al., 2010). A full characterization of various crystal forms of an active pharmaceutical ingredient (API) may reveal desired physical form. Thus, it is relevant to pharmaceutical industry. Nitrofurantoin {(E)-1-[(5-nitro-2-furyl)methylideneamino]imidazoldine-2,4-dione} is an antibacterial agent used in the treatment of genitourinary tract infections. It exists in both anhydrous (α-and β-) and hydrate forms (Forms I and II) (Pienaar et al., 1993a(Pienaar et al., , 1993bBertolasi et al., 1993), and literature findings show that nitrofurantoin has poor physical properties (Otsuka et al., 1991;Caira et al., 1996). We have recently reported a 1:1 co-crystal involving nitrofurantoin and 4-hydroxybenzoic acid and shown that co-crystal displayed superior physicochemical and photo-stability to that of nitrofurantoin. However, co-crystallization attempt of nitrofurantoin with fumaric acid in methanol instead yielded the title pseudopolymorph, nitrofurantoin methanol monosolvate. It was reported that this API is known to form inclusion complexes with dimethylformamide, dimethyl sulfoxide and dimethylacetamide (Caira et al., 1996;Tutughamiarso et al., 2011). Herein we report the structural features of a 1:1 pseudopolymorph involving nitrofurantoin and methanol (Fig. 1).
Thermogravimetric analysis (TGA traces) of the title compound is shown in Fig. 2. The measured weight loss (11.6% w/w) in the temperature range of 110-140 °C is in agreement with the stoichiometric weight content for a methanol monosolvate (11.8% w/w).
Single crystal X-ray diffraction analysis reveals that the crystal structure contains one molecule each of nitrofurantoin and methanol in the asymmetric unit ( Fig. 1). It has crystallized in the monoclinic crystal system with P2 1 /c space group.

Experimental
The title psuedopolymorph was obtained by evaporative crystallization during attempts to co-crystallize a commercially available (purchased from Aldrich) nitrofurantoin (β-form, 119 mg, 0.5 mmol) with fumaric acid (58 mg, 0.5 mmol) in methanol (25 ml) at ambient conditions. The yellow needle shaped crystals suitable for single-crystal X-ray diffraction were obtained in three days.

Refinement
All H atoms bonded to C, N, O atoms were located in a difference map and allowed to ride on their parent atoms in the refinement cycles. Fig. 1. A perspective view showing the molecular structures of nitrofurantoin and methanol, with atom labels and 50% probability displacement ellipsoids for non-H atoms. The dashed line shows the N-H···O hydrogen bond. Fig. 2. TGA traces showed that there was a weight loss of 11.6% (w/w), which can be attributed to a methanol solvate.   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 Rfactors(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.