Comment

The majority of structurally determined phthalimidine systems are either N-substituted or have a hydroxy substituent at the 3-position (McNab et al., 1997; Mukherjee et al., 2000). The title compound, (I), synthesized from L-leucine and ortho-phthalaldehyde (Allin et al., 1996), forms part of a structural study of phthalimidines (Brady et al., 1998; Gallagher et al., 2000; Gallagher & Brady, 2000; Gallagher & Murphy, 2001).

The molecular structure of (I) is depicted in Fig. 1 (S configuration) and selected dimensions are given in Table 1. The geometric data are normal (McNab et al., 1997) and in agreement with expected values (Allen, 2002). The five- and six-membered rings of the isoindole group are coplanar [dihedral angle between rings = 1.0 (2)°], and the isoindolinone atom O3 is 0.022 (5) Å from the C₄N ring plane; this ring is oriented at 82.5 (5)° to the major orientation of the CCO₂ plane (O1A/O2A/C1/C2).

Molecules of (I) exhibit CO₂H group disorder about the C-CO₂ axis with site occupancies of 0.79 (5):0.21 (5) for the major/minor sites, respectively. Conventional CO₂H dimeric hydrogen bonding [R₂²(8) ring] is not present as a requirement of symmetry; rather, the primary hydrogen bonding as an (O-HO-H)_n chain along [010] involving O1A/B-H1A/BO3ⁱ (Table 1) is described by a C(7) motif (Grell et al., 1999). The closest H atoms to the carbonyl O2A/B are at contact distances, e.g. H7O2Aⁱⁱⁱ is 2.71 Å, with C7-H7O2Aⁱⁱⁱ = 136° (symmetry codes iii as in Table 2). Disorder is facilitated on geometric grounds as O2 can rotate about the C1-C2 axis without greatly affecting the O1A/B-H1A/BO3ⁱ interaction distance (Fig. 2).

Combination of the O-HO=C_iso C(7) motif with a C(5) motif (from C10-H10AO3ⁱⁱ) generates a two-dimensional sheet comprising R₄³(20) rings as C(7)C(5)[R₄³(20)]; modest (arene)C-H(arene) interactions (Nishio, 2004) link these sheets (Fig. 3 and Table 2).

Compound (I) and the L-norvaline derivative, (II), C₁₃H₁₅NO₃, (2S)-2-(1-oxo-1H-2,3-dihydroisoindol-2-yl)pentanoic acid (Gallagher & Brady, 2000), both crystallize in space group P2₁2₁2₁ with similar cell dimensions. The corresponding atom coordinates and molecular conformations are comparable and hence the crystal structures are isomorphous. Molecules of (I) and (II) differ in their respective alkyl chains with the (CH₃)₂CHCH₂- group in (I) occupying a similar volume as the disordered CH₃CH₂CH₂- group in (II). The solid-state (KBr disk) C=O stretching vibrations are similar, 1736, 1638 cm^-1 in (I) and 1730, 1649 cm^-1 in (II), highlighting the analogous environments of both C=O groups in (I) and (II).

Figure 1 A view of (I), with the atomic numbering scheme; displacement ellipsoids are drawn at the 30% probability level. Both disorder components are shown.

Figure 2 Two molecules of (I), with atoms depicted as their van der Waals spheres, with C7 (C-HOiii contact) and C8 [C-H(arene)iii] labels.

Figure 3 A view of the C(7)C(5)[R43(20)] sheet in (I) with the unit-cell outline (symmetry codes as in Table 2); H atoms not involved in hydrogen bonding have been omitted for clarity.

Experimental

The title compound (I) was prepared by the overnight reaction of L-leucine and o-phthalaldehyde in refluxing CH₃CN under N₂ (Allin et al., 1996). Filtration of the hot solution and subsequent slow cooling of the filtrate allowed the isolation of block-like colourless crystals. M.p. 485-487 K (uncorrected).

Crystal data

C14H17NO3 Mr = 247.29 Orthorhombic, P 21 21 21 a = 5.8790 (5) Å b = 12.5223 (16) Å c = 18.029 (3) Å V = 1327.3 (3) Å3 Z = 4 Dx = 1.237 Mg m-3 Mo K radiation = 0.09 mm-1 T = 294 (1) K Block, colourless 0.35 × 0.25 × 0.15 mm

Data collection

Enraf-Nonius CAD-4 diffractometer -2 scans Absorption correction: none 2394 measured reflections 1373 independent reflections 889 reflections with I > 2(I) Rint = 0.053 max = 25.0° 3 standard reflections frequency: 120 min intensity decay: 1%

Refinement

Refinement on F2 R[F2 > 2(F2)] = 0.044 wR(F2) = 0.080 S = 1.00 1373 reflections 185 parameters H-atom parameters constrained w = 1/[2(Fo2) + (0.0312P)2] where P = (Fo2 + 2Fc2)/3 (/)max < 0.001 max = 0.13 e Å-3 min = -0.13 e Å-3 Extinction correction: SHELXL97 Extinction coefficient: 0.013 (2)

Table 1 Selected torsion angles (°) C3-N1-C2-C11 133.9 (3) C3-N1-C2-C1 -97.4 (4) O3-C3-N1-C2 -1.6 (5) O1A-C1-C2-C11 -51.2 (9)

Table 2 Hydrogen-bond geometry (Å, °) D-HA D-H HA DA D-HA O1A-H1AO3i 0.82 1.83 2.634 (9) 168 C10-H10AO3ii 0.97 2.54 3.366 (4) 144 C8-H8Cg1iii 0.93 2.74 3.473 (4) 137 C2-H2O3 0.98 2.38 2.812 (4) 106 Symmetry codes: (i) ; (ii) x+1, y, z; (iii) .

In the absence of significant anomalous dispersion effects, Friedel equivalents were merged prior to the final refinement cycles. The absolute configuration can be inferred from the known absolute configuration of the L-leucine starting material. H atoms were treated as riding atoms using the SHELXL97 (Sheldrick, 1997) defaults [at 294 (1) K], with C-H distances from 0.93 to 0.98 Å and O-H = 0.82 Å, and with U_iso(H) from 1.2 to 1.5 times U_eq(C,O).

Data collection: CAD-4 (Enraf-Nonius, 1992); cell refinement: SET4 and CELDIM (Enraf-Nonius, 1992); data reduction: DATRD2 in NRCVAX96 (Gabe et al., 1989); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: NRCVAX96 and SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 and WORDPERFECT macro PREP8 (Ferguson, 1998).