Comment

Hydrogen bonding is an important force central to the functioning of several complex and large biomolecules such as enzymes, DNA and RNA. It plays a major role in the design of novel supramolecular architectures and allows recognition among many organic molecules. Crystal engineering pertains to the directionality of hydrogen bonds and the ways in which hydrogen bonding influences crystal geometries depending on their strengths (Desiraju, 2011; Adam et al., 2010). Phenol compounds can exhibit inter- and intramolecular hydrogen bonding depending on the nature and position of additional functional groups. The electronic nature and the ortho, para or meta position of the substituent strongly influences the acidity of the phenolic H atom and hence the strength of the hydrogen bond.

2,2-Bis(ethoxycarbonyl)vinyl (BECV) derivatives are important intermediates useful in the synthesis of various nitrogen- and oxygen-containing heterocycles, as ligands in inorganic metal complexes and in the detection of amino acids. BECV-amine derivatives are mainly used as building blocks for the synthesis of a variety of bioactive nitrogen-containing

heterocycles such as pyrazoles, 4-oxoquinoline-3-carboxylic acid esters, pyrimidines, pyrimido[1,2-a]pyrimidines, 3H,5H-pyrrolo[3,2-d]pyrimidines and pyrido[2,3-d]pyrimidines (Johnson & Ambler, 1911; Fustero et al., 2011; Niedermeier et al., 2009; Yang et al., 2009; Candeias et al., 2009; Petric et al., 1983; Furneaux & Tyler, 1999).

Simple diethyl 2-[(alkyl/aryl)aminomethylidene]malonate (N-BECV) derivatives are biologically active compounds. Steck (1962) observed that N-BECV derivatives of diisopropylamine, piperidine {diethyl 2-[(piperidin-1-yl)methylidene]malonate, see (1) in Scheme 2}, pyrrolidine and morpholine

are central nervous system stimulants. Similarly, Santilli et al. (1964) prepared a number of enamine derivatives containing the N-BECV unit, such as a 4-(aminomethyl)benzoic acid derivative, diethyl 2-({[3-(dimethylamino)propyl]amino}methylidene)malonate [see (2) in Scheme 2] and diethyl 2-{[(diphenylmethoxy)amino]methylidene}malonate [see (3) in Scheme 2], and established their muscle relaxation and sedative properties. In addition, N-BECV derivatives show a very low cytotoxicity to normal cells.

Recently, we have demonstrated that N-BECV can be used as a chemo-selective amine-protecting group useful for several sensitive organic functional group transformations (Ilangovan & Ganesh Kumar, 2010). In a continuation of this work, we studied the crystal structures of diethyl 2-[(2-hydroxyanilino)methylidene]malonate, (I), and diethyl 2-[(4-hydroxyanilino)methylidene]malonate, (II), and the effect of hydroxy-group substitution on their supramolecular architectures. To the best of our knowledge, single-crystal structures of BECV derivatives have not been reported previously.

Compounds (I) and (II) (Fig. 1) are regioisomers. Compound (I) occupies a crystallographic mirror plane and is totally planar, with the exception of a disordered ethoxy group where atom C13 occupies alternate positions just off the mirror plane. The benzene ring in compound (II) is not constrained to be planar by any crystallographic symmetry, but is essentially planar, with an r.m.s. deviation of the ring atoms from their mean plane of 0.016 Å. The angles between the plane of the aminophenol ring and the plane of the vinylic double bond are 0 and 33.59 (12)° in (I) and (II), respectively. In both compounds, the C1-N1 (C_ar-N) bonds (Table 1) are shorter than a normal N-C bond (1.336 Å; Allen et al.. 1987) because of conjugation between -electrons in the vinylic double bond and the lone pair electrons of the N atom. The vinylic C7-C8 bond lengths are similarly longer than normal vinylic C-C bonds (1.316 Å; Allen et al.. 1987).

The presence of a phenolic -OH group at the ortho position to the amine group in compound (I) favours strong bifurcated intramolecular hydrogen bonds between the amine group and the hydroxy O atom, O1, and one of the ester carbonyl O atoms, O4 (Table 2). This gives rise to S(6) and S(5) ring motifs (Fig. 2) (Bernstein et al., 1995) and helps in achieving rigorous planarity. The molecules are linked into extended chains, which run parallel to the b axis, by an intermolecular hydrogen bond between the hydroxy group and the carbonyl O atom of the second ester group in an adjacent molecule. This interaction has a graph-set motif of C(9). No interactions are observed between the chains.

In the case of (II), two hydrogen-bond interactions (N1-H1NO4 and O1-H1OO2ⁱ; symmetry code as in Table 3) are observed, the former intramolecular interaction gives rise to an S(6) ring motif (Table 3). The latter interaction gives rise to an extended chain which runs parallel to the a axis and has a graph-set motif of C(11) (Fig. 3). In addition to head-to-tail hydrogen bonding, there is a macrocyclic R₂²(26) dimer motif formed by a C11-H11CO1ⁱⁱ interaction (Table 3) between two adjacent one-dimensional chains (Fig. 4). This gives rise to a ladder-like structure (Figs. 4b and 5). Neither compound shows any significant centroid-centroid or C-H interactions.

In conclusion, we have studied crystal structure properties such as motifs, chains, the nature of hydrogen bonding and other interactions of the title compounds (I) and (II). Variations in the ortho and para substitution of hydroxy groups was analysed. The presence of an -OH group adjacent to an -NH group favours bifurcated hydrogen bonding and the formation of S(6) and S(5) ring motifs, and gives rise to strict planarity for compound (I). In a supramolecular framework it gives rise to a layer-like structure. In the case of compound (II), a S(6) ring and a macrocyclic R₂²(26) ring motif were observed between chains. Both compounds form a head-to-tail one-dimensional hydrogen-bonded chain. We believe that this study will be helpful in understanding the ability of these molecules to interact with biological systems. The compounds may be useful synthons in the formation of metal complexes and different hereocyclic compounds.

Experimental

Diethyl 2-(ethoxymethylidene)malonate (1 equivalent) was added to a solution of 2- or 4-aminophenol (1 equivalent) in ethanol (5 × w/v) and the resulting solution stirred for 15 min at room temperature (301 K) (Ilangovan & Ganesh Kumar, 2010). After completion of the reaction, the ethanol was evaporated under reduced pressure to give compound (I) or (II) as a white solid in quantitative yield [99% yields; m.p. 402 and 412 K for (I) and (II), respectively]. Good quality single crystals of (I) and (II) suitable for diffraction analysis were obtained from hexane and ethyl acetate mixtures (8:2 v/v).

For compound (I), the amino and hydroxy H atoms were located in a difference map and refined isotropically. All other H atoms, were placed in their geometrically idealized positions and refined using a riding model, with C-H = 0.93 (aromatic and methyl) or 0.97 Å (methylene), O-H = 0.82 Å and N-H = 0.86 Å, and with U_iso(H) = 1.5U_eq(C,O) for the methyl groups and the hydroxy group in (II), and U_iso(H) = 1.2U_eq(C,N) otherwise.

For both compounds, data collection: SMART (Bruker, 2008); cell refinement: SMART; data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON.

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Supplementary data for this paper are available from the IUCr electronic archives (Reference: FN3116 ). Services for accessing these data are described at the back of the journal.

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