Crystal structures of methyl 3-(4-isopropylphenyl)-1-methyl-1,2,3,3a,4,9b-hexahydrothiochromeno[4,3-b]pyrrole-3a-carboxylate, methyl 1-methyl-3-(o-tolyl)-1,2,3,3a,4,9b-hexahydrothiochromeno[4,3-b]pyrrole-3a-carboxylate and methyl 1-methyl-3-(o-tolyl)-3,3a,4,9b-tetrahydro-1H-thiochromeno[4,3-c]isoxazole-3a-carboxylate

Three thiochromeno[4,3-b]pyrrole esters have very similar conformations. Structurally two of the compounds differ only by the substituent on the benzene ring, i.e. 4-isopropylphenyl and o-tolyl, while two of the compounds differ only in that one has a pyrrole ring and one has an isoxazole ring.


Chemical context
Pyrrole derivatives are of considerable synthetic importance due to their extensive use in drug discovery (Toja et al., 1987) which is linked to their pharmacological activity such as antiinflammatory (Muchowski et al., 1985), cytotoxicity (Dannhardt et al., 2000) and their use in the treatment of hyperlipidemias (Holub et al., 2004) and as antitumour agents (Krowicki et al., 1988). Other pyrrole-containing heterocyclic compounds have been reported previously for biological studies (Almerico et al., 1998). Pyrrole derivatives have biological activity such as COX-1/COX-2 inhibitors (Dannhardt et al., 2000) as well as cytotoxic activity against a variety of marine and human tumour models (Evans et al., 2003). Isoxazoline derivatives have been shown to be efficient precursors for the preparation of many synthetic intermediates including -amino alcohols and -hydroxy ketones (Kozikowski, 1984). They display interesting biological properties such as herbicidal, plant-growth regulatory and antitumour activities (Howe & Shelton, 1990). Chromenopyrrole compounds are used in the treatment of impulsive disorders (Caine & Koob, 1993). Continuing our interest in such compounds, we have synthesized the title compounds and report herein on their crystal structures. ISSN 2056-9890

Structural commentary
The title compounds (I) and (II) differ only by the substituent on the benzene ring; 4-isopropylphenyl in (I) and o-tolyl in (II). Compounds (II) and (III) differ only in that (II) has a pyrrole ring while (III) has an isoxazole ring.
The molecular structure of compound (I) is shown in Fig. 1. The five-membered methyl-substituted pyrrole ring adopts an envelope conformation with atom C9 as the flap, deviating from the mean plane defined by the plane of the other ring atoms by 0.0167 Å . The puckering parameters of this ring are q 2 = 0.4713 (15) Å and ' 2 = 41.27 (19) . The thiopyran ring has a half-chair conformation, with the lowest asymmetry parameters ÁC2(S1-C7) = 8.34 (16) Å . The mean plane of the pyrrole ring makes dihedral angles of 57.07 (9) and 63.29 (10) with the mean plane of the thiopyran ring and the benzene ring, respectively.
The molecular structure of the compound (II) is illustrated in Fig. 2. The bond lengths and bond angles are similar to those in compound (I). The pyrrole ring (N1/C8-C12) adopts an envelope conformation with atom C9 atom as the flap having asymmetry parameters (Nardelli, 1983) ÁCS(C9) = 4.51 Å and with puckering parameters q 2 = 0.4673 (18) Å , ' 2 = 223.5 (2) . As in (I), the thiopyran ring has a half-chair conformation. The mean plane of the pyrrole ring is inclined to thiopyran ring mean plane and the benzene ring by 58.98 (9) and 67.75 (11) , respectively. The carboxylate group assumes an extended conformation, as can be seen from the C8-C13-O2-C14 torsion angle of 175.4 (2) .
The molecular structure of molecule (III) is shown in Fig. 3. The isoxazole ring (N1/O3/C11/C8/C9) has a twist conformation about bond C9-C8: puckering parameters q 2 = The molecular structure of compound (I), showing the atom labelling. Displacement ellipsoids are drawn at the 30% probability level.

Figure 2
The molecular structure of compound (II), showing the atom labelling. Displacement ellipsoids are drawn at the 30% probability level.

Supramolecular features
In the crystals of compounds (I), (II) and (III), there are no classical hydrogen bonds present. Only in compound (I) is there a C-HÁ Á Á interaction present, and molecules are linked by a pair of these interactions forming inversion dimers (Table 1 and Fig. 4).  Table 1 Hydrogen-bond geometry (Å , ) for (I).

Database survey
Cg3 is the centroid of the C1-C6 ring.

Figure 4
A view along the b axis of the crystal packing of compound (I). The dashed cyan lines represent the C-HÁ Á Ácentroid distances (see Table 1).

Synthesis and crystallization
Compound (I): To a solution of methyl (E)-2-{[(2-formylphenyl)thio]methyl}-3-phenylacrylate (1 mmol) and sarcosine (1.2 mmol) in acetonitrile (10 ml), was added pyridine (0.2 mmol) and the mixture was refluxed until completion of the reaction (monitored by TLC). The crude product was subjected to column chromatography on silica gel (100-200 mesh) using petroleum ether-ethyl acetate (9:1) as eluent, which successfully provided the pure product as a colourless solid. The product was dissolved in chloroform and heated for 2 min. The resulting solution were allowed to evaporate slowly at room temperature and yielded colourless block-like crystals of compound (I).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The C-bound H atoms were positioned geometrically (C-H = 0.93-0.98 Å ) and allowed to ride on their parent atoms, with U iso (H) = 1.5U eq (C) for methyl H atoms and 1.2U eq (C) for other H atoms. The isopropyl group in compound (I), atoms C19-C21, is disordered over two sets of sites and has a refined occupancy ratio of 0.586 (13):0.414 (13).
Special details Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. 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.

Hydrogen-bond geometry (Å, º)
Cg3 is the centroid of the C1-C6 ring. 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.