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The title compounds, C12H13NO4, are derived from L-threonine and DL-threonine, respectively. Hydro­gen bonding in the chiral derivative, (2S/3R)-3-hydroxy-2-(1-oxoisoindolin-2-yl)­butanoic acid, consists of O—Hacid...Oalkyl—H...O=Cindole chains [O...O 2.659 (3) and 2.718 (3) Å], Csp3—H...O and three C—H...πarene interactions. In the (2R,3S/2S,3R) racemate, conventional carboxylic acid hydrogen bonding as cyclical (O—H...O=C)2 [graph set R22(8)] is present, with Oalkyl—H...O=Cindole, Csp3—H...O and C—H...πarene interactions. The COOH group geometry differs between the two forms, with C—O, C=O, C—C—O and C—C=O bond lengths and angles of 1.322 (3) and 1.193 (3) Å, and 109.7 (2) and 125.4 (3)°, respectively, in the chiral structure, and 1.2961 (17) and 1.2210 (18) Å, and 113.29 (12) and 122.63 (13)°, respectively, in the racemate structure. The O—C=O angles of 124.9 (3) and 124.05 (14)° are similar. The differences arise from the contrasting COOH hydrogen-bonding environments in the two structures.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270199015619/bm1380sup1.cif
Contains datablocks global, I, II

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270199015619/bm1380Isup2.hkl
Contains datablock I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270199015619/bm1380IIsup3.hkl
Contains datablock II

Comment top

The study of biologically active molecules is of primary importance in medicinal chemistry. Many inhibitors are based on modified amino acids which incorporate the basic structural features determining normal enzyme-substrate interactions. Phthalimidine (isoindolin-1-one) derivatives often display biological activity as potential antiinflammatory agents and antipsychotics (Norman et al., 1993; Allin et al., 1996). The majority of structurally determined phthalimidine systems are either N-substituted or substituted at the 3-position (McNab et al., 1997; Kundu et al., 1999). Threonine and its derivatives have attracted considerable interest, not least due to the alkyl hydroxy group which can participate in binding, intermolecular interactions and as a linking group in proteins. The title compounds, (2S/3R)-3-hydroxy-2-(1-oxoisoindolin-2-yl)butanoic acid, (I), and (2R,3S/2S,3R)-3-hydroxy-2-(1-oxoisoindolin-2-yl)butanoic acid, (II), synthesized from the chiral L and racemic DL forms of threonine, respectively, constitute part of a study of the hydrogen-bonding interactions and anion recognition properties of synthetic amino acid derivatives (Brady et al., 1998; Dalton et al., 1999; Gallagher & Murphy, 1999; Gallagher et al., 1999a,b). \scheme

A view of molecule (I) (SR configuration) is shown in Fig. 1 and selected dimensions are in Table 1. Molecule (II) is depicted similarly in Fig. 2, with selected dimensions in Table 3. The bond lengths and angles in the isoindoline group of both structures are similar to those reported previously (McNab et al., 1997; Kundu et al., 1999) and are in agreement with expected values (Orpen et al., 1994). The angles between the five- and six-membered rings of the isoindoline systems are 0.66 (18)° in (I) and 1.13 (11)° in (II), and the maximum deviation from planarity for an atom in either ring plane is 0.0179 (17) Å for N1 in (I) and 0.0168 (9) Å for N1 in (II), with the carbonyl O3 atom 0.071 (4) Å from the C4N ring plane in (I), and 0.061 (2) Å in (II). The carboxylic acid CCO2 plane is almost perpendicular to the C4N ring plane [72.30 (11)° in (I) and 66.40 (6)° in (II)] and to the C12/C11/O4 (H3CCOH) plane [76.5 (2)° in (I) and 64.50 (8)° in (II)].

There are distinct differences in the carboxylic acid bond lengths and angles of (I) and (II). The C—O and C=O bond lengths are 1.322 (3) and 1.193 (3) Å in (I), and 1.2961 (17) and 1.2210 (18) Å in (II), respectively. The O—C—C2 and O=C—C2 angles are 109.7 (2) and 125.4 (3)° in (I), differing considerably from 113.29 (12) and 122.63 (13)° in (II). However, the O=C—O bond angles are similar, at 124.9 (3) and 124.05 (14)°, respectively. This suggests that the differences may be influenced by their different hydrogen-bonding environments (Tables 2 and 4), resulting in a twist in the COOH groups of ca 3°. The carboxylic group geometry in (I) is similar to that reported in a DL-phenylalanine derivative, (III) (Brady et al., 1998) and in a meta-tyrosine derivative, (IV) (Gallagher & Murphy, 1999). The C—O and C=O bond lengths are 1.314 (2) and 1.194 (2), and 1.328 (2), 1.196 (2) Å, in (III) and (IV), respectively, with O—C=O angles of 124.00 (18) and 124.3 (3)° in (III) and (IV), respectively. The O—C—C2 and O=C—C2 angles in (III) and (IV) are intermediate between the values in (I) and (II), at 112.05 (16) and 123.95 (18)° for (III), and 110.17 (18) and 125.55 (19)° for (IV); these values for (IV) are close to those for (I) above.

The indole C=O and hydroxy Csp3—O bond lengths of 1.232 (3) and 1.427 (3) Å, and 1.2350 (17) and 1.4187 (17) Å are similar in (I) and (II), respectively, [1.239 (2) and 1.236 (2) Å for the indole C=O bond lengths in (III) and (IV), respectively]. However, the O4—C11—C2 and C1—C2—C11 angles differ notably, with values of 110.5 (2) and 112.7 (2)° in (I), and 105.52 (11) and 110.14 (11)° in (II), and this is also indicative of dissimilar hydrogen-bonding environments. Torsion angle differences are evident, with N1—C2—C11—O4 = 78.1 (3)° in (I) and 66.92 (15)° in (II), reflecting the different participation of the alkyl O—H group in hydrogen bonding in the two structures.

The hydrogen-bonding arrangements are maximized in both structures and related to those in (III) and (IV) (Brady et al., 1998; Gallagher & Murphy, 1999). The hydrogen bonding in (I) and (II) is dominated by O—H···O, C—H···O and C—H···πarene interactions (Tables 2 and 4, Figs. 3 and 4). The primary hydrogen bonding in (I) involves OacidH···OalkylH···O=Cisoindole chains [O···O 2.659 (3) and 2.718 (3) Å], similar to the primary hydrogen-bonded chain in the meta-tyrosine structure (Gallagher & Murphy, 1999), where the O···O distances are 2.668 (2) and 2.653 (2) Å. The O—Hi···O—H···O=Cii chain in (I) forms a one-dimensional network in the a axis direction, with hydrogen-bonded rings [graph set R33(15)] consisting of one alkyl O—H and two acid O—H donors and an indole O=C and two alkyl O—H groups as acceptors between three molecules [symmetry codes: (i) 1/2 + x, 1/2 - y, 2 - z; (ii) 1 + x, y, z]. The C10—H10A···O3ii hydrogen bond [C···O 3.513 (4) Å] further generates a hydrogen-bonded ring system [graph set R12(8)], with an alkyl O—H and a Csp3—H as donors and the indole O=C as an acceptor along the a axis direction [H4···O3ii···H10A 66°]. The carboxylic acid oxygen O2 only forms a weak C—H···O contact in (I). The C—H···πarene interactions complete the intermolecular interactions, forming a three-dimensional network in the crystal structure of (I) with two (C11—H11/C12—H12C)···πindole contacts participating in a relay of C—H···πarene interactions.

Compound (II) shows some interesting differences to (I). Classical COOH hydrogen bonding arises [to form dimers; graph set R22(8)] about inversion centres as cyclical O—H···O=C hydrogen bonds involving both O1 and O2 (Ferguson et al., 1995). The alkyl hydroxy group O4—H···O=C3 links these dimers to form a two-dimensional network, as depicted in Fig. 4. Weaker CH···O=Cindole and Csp3—H···πarene interactions complete the hydrogen bonding, thus forming a three-dimensional network. The contrast in the carboxylic acid geometry between (I) and (II) can be explained by the dissimilar participation of O2 in the hydrogen bonding. The primary COOH hydrogen bonding in (II) [graph set R22(8)] differs from that reported in the DL-phenylalanine structure (III), where pairwise intermolecular OacidH···Oindole and CareneH···Ocarboxylate interactions form a hydrogen-bonded ring [graph set R22(9)], and from that in the structures of (I) and DL-meta-tyrosine (IV), which contain OacidH···OH···O=Cindole chains.

The volumes per atom in (I) and (II) differ, with a value of 16.51 Å3 per non-H atom for (I) and 17.04 Å3 for (II), reflecting differing packing considerations and the extra interactions present in (I). Examination of the structures with PLATON (Spek, 1998) shows that there are no solvent accessible voids in either crystal lattice.

Crystal engineering studies continue to rely on stronger hydrogen bonds for the design and synthesis of three-dimensional structures (Aakeröy et al., 1999). However, a thorough understanding of the control and exploitation of X—H···πarene interactions (X = C, N or O) remains an elusive goal (Braga et al., 1998). Theoretical calculations on C—H···πarene interactions have been reported in several organic systems, including an estimation of the binding energy between the C—H donor and the aromatic π cloud (Samanta et al., 1998), as well as database studies (Malone et al., 1997). The role of such interactions in biological structures has also been detailed by Umezawa & Nishio (1998). However, in (I) and (II), the primary hydrogen bonding is considered prior to analysis of the weaker interactions. The stronger hydrogen bonds form a primary array which is linked into networks by the weaker interactions in both structures. Further comparative studies are in progress on related phthalimidines.

Experimental top

Compound (I) was prepared by the overnight reaction of L-threonine 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 colourless plates of (I) (m.p. 458–460 K, uncorrected). Spectroscopic analysis: IR (KBr, cm-1): (νOH) 3256, (νCO) 1748, 1656; 1H NMR (400 MHz, δ, d6 DMSO): 1.07 (d, 3H, CH3), 4.46 (m, 1H, CH), 4.69 (s, 2H, CH2), 4.80 (d, 1H, CH), 5.29 (br s, 1H, O—H), 7.46–7.52, 7.61–7.66, 7.71–7.73 (m, 4H, C6H4). Compound (II) was prepared as detailed for (I) above, using DL-threonine as the starting material, and colourless blocks of (II) were obtained from solution (m.p. 424–427 K, uncorrected). Spectroscopic analysis: IR (KBr, cm-1): (νOH) 3234, (νCO) 1759, 1644; 1H NMR (400 MHz, δ, d6 DMSO): 1.07 (m, 3H, CH3), 4.45 (m, 1H, CH), 4.68 (s, 2H, CH2), 4.73 (d, 1H, CH), 5.31 (br s, 1H, O—H), 7.48–7.52, 7.60–7.66, 7.71–7.73 (m, 4H, C6H4).

Refinement top

For both compounds, all H atoms bound to C were treated as riding, with the SHELXL97 (Sheldrick, 1997a) defaults for C—H distances and with Uiso(H) = 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C) for others. For (I), H atoms bound to O were refined with isotropic displacement parameters, while for (II), H atoms bound to O were located from difference Fourier maps in the penultimate stages of refinement and subsequently treated as rigid rotating groups with Uiso(H) = 1.5Ueq(O). (Please check new text.)

Computing details top

For both compounds, data collection: CAD-4-PC Software (Enraf-Nonius, 1992); cell refinement: CAD-4-PC Software; data reduction: NRCVAX96 (Gabe et al., 1989); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997b); program(s) used to refine structure: NRCVAX96 and SHELXL97 (Sheldrick, 1997a); molecular graphics: ORTEPIII (Burnett & Johnson, 1996), ORTEX (McArdle, 1995) and PLATON (Spek, 1998); software used to prepare material for publication: NRCVAX96, SHELXL97 and PREP8 (Ferguson, 1998).

Figures top
[Figure 1] Fig. 1. A view of (I) with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 2] Fig. 2. A view of (II) with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 3] Fig. 3. A view of the intermolecular interactions in (I).
[Figure 4] Fig. 4. A view of the intermolecular interactions in (II).
(I) (2S/3R)-3-hydroxy-2-(1-oxoisoindolin-2-yl)butanoic acid top
Crystal data top
C12H13NO4Dx = 1.392 Mg m3
Mr = 235.23Melting point: 459 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.7107 Å
a = 6.2209 (6) ÅCell parameters from 25 reflections
b = 11.9726 (13) Åθ = 9.7–19.6°
c = 15.0705 (12) ŵ = 0.11 mm1
V = 1122.5 (2) Å3T = 294 K
Z = 4Plate, colourless
F(000) = 4960.32 × 0.14 × 0.12 mm
Data collection top
Enraf-Nonius CAD-4
diffractometer
Rint = 0.020
Radiation source: X-ray tubeθmax = 25.0°, θmin = 2.2°
Graphite monochromatorh = 07
ω/2θ scansk = 1414
3932 measured reflectionsl = 1717
1967 independent reflections3 standard reflections every 120 min
1441 reflections with I > 2σ(I) intensity decay: variation <1%
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.040Calculated w = 1/[σ2(Fo2) + (0.0538P)2]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.096(Δ/σ)max = 0.001
S = 1.01Δρmax = 0.16 e Å3
1967 reflectionsΔρmin = 0.15 e Å3
163 parametersExtinction correction: SHELXL97 (Sheldrick, 1997a), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.011 (3)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983)
Secondary atom site location: difference Fourier mapAbsolute structure parameter: not reliably determined
Crystal data top
C12H13NO4V = 1122.5 (2) Å3
Mr = 235.23Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 6.2209 (6) ŵ = 0.11 mm1
b = 11.9726 (13) ÅT = 294 K
c = 15.0705 (12) Å0.32 × 0.14 × 0.12 mm
Data collection top
Enraf-Nonius CAD-4
diffractometer
Rint = 0.020
3932 measured reflections3 standard reflections every 120 min
1967 independent reflections intensity decay: variation <1%
1441 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.040H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.096Δρmax = 0.16 e Å3
S = 1.01Δρmin = 0.15 e Å3
1967 reflectionsAbsolute structure: Flack (1983)
163 parametersAbsolute structure parameter: not reliably determined
0 restraints
Special details top

Geometry. Specific hydrogen bonds & contacts (with e.s.d.'s except fixed and riding H) ============================================================== D—H H···A D···A D—H···A Interaction ============================================================== 0.81 (4) 1.87 (4) 2.659 (3) 162 (4) O1—H1···O4_$2 0.82 (4) 1.90 (4) 2.718 (3) 174 (4) O4—H4···O3_$3 0.97 2.57 3.513 (4) 165.1 C10—H10A···O3_$3 0.93 3.11 3.781 (4) 130.2 C5—H5···C4_$4 0.93 3.07 3.941 (3) 156.0 C5—H5···C5_$4 0.93 3.06 3.913 (4) 153.3 C5—H5···C6_$4 0.93 3.11 3.743 (4) 127.3 C5—H5···C7_$4 0.93 3.19 3.618 (4) 110.2 C5—H5···C8_$4 0.93 3.19 3.638 (4) 111.7 C5—H5···C9_$4 0.98 3.26 3.879 (4) 122.5 C11—H11···C4_$5 0.98 2.98 3.798 (4) 141.7 C11—H11···C5_$5 0.98 2.76 3.726 (4) 167.6 C11—H11···C6_$5 0.98 2.91 3.782 (4) 149.3 C11—H11···C7_$5 0.98 3.22 3.882 (4) 126.3 C11—H11···C8_$5 0.98 3.38 3.920 (4) 116.9 C11—H11···C9_$5 0.96 3.28 4.145 (4) 151.4 C12—H12C···N1_$5 0.96 3.10 3.777 (4) 128.7 C12—H12C···C3_$5 0.96 2.91 3.508 (4) 121.8 C12—H12C···C4_$5 0.96 2.96 3.730 (4) 138.2 C12—H12C···C9_$5 0.96 3.21 4.146 (4) 165.9 C12—H12C···C10_$5 0.93 2.81 3.554 (4) 137.4 C7—H7···O2_$6

The interaction details are also described in the hydrogen bonding table.

Mean plane data ex-SHELXL97 for molecule (I) ############################################

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

6.1626(0.0015)x + 1.6324(0.0187)y + 0.1081(0.0230)z = 3.9677(0.0215)

* -0.0031 (0.0008) O1 * -0.0040 (0.0010) O2 * 0.0098 (0.0026) C1 * -0.0027 (0.0007) C2 1.0724 (0.0046) C11 - 0.0149 (0.0047) N1

Rms deviation of fitted atoms = 0.0057

-2.5506(0.0060)x + 9.1968(0.0082)y + 7.4112(0.0141)z = 6.3865(0.0084)

Angle to previous plane (with approximate e.s.d.) = 72.67 (10)

* -0.0051 (0.0018) C4 * -0.0011 (0.0020) C5 * 0.0068 (0.0020) C6 * -0.0064 (0.0020) C7 * 0.0002 (0.0020) C8 * 0.0055 (0.0018) C9 0.0088 (0.0043) N1

Rms deviation of fitted atoms = 0.0049

-2.5910(0.0079)x + 9.2245(0.0101)y + 7.2729(0.0172)z = 6.2940(0.0127)

Angle to previous plane (with approximate e.s.d.) = 0.66 (18)

* -0.0179 (0.0017) N1 * 0.0154 (0.0016) C3 * -0.0065 (0.0016) C4 * -0.0035 (0.0016) C9 * 0.0124 (0.0016) C10 0.0713 (0.0040) O3 1.4338 (0.0054) C1 0.0604 (0.0045) C2

Rms deviation of fitted atoms = 0.0124

6.1626(0.0015)x + 1.6324(0.0187)y + 0.1081(0.0230)z = 3.9677(0.0215)

Angle to previous plane (with approximate e.s.d.) = 72.30 (11)

* -0.0031 (0.0008) O1 * -0.0040 (0.0010) O2 * 0.0098 (0.0026) C1 * -0.0027 (0.0007) C2 1.0724 (0.0046) C11 - 0.0149 (0.0047) N1

Rms deviation of fitted atoms = 0.0057

2.0571(0.0200)x - 8.6012(0.0129)y + 9.2232(0.0343)z = 8.3712(0.0188)

Angle to previous plane (with approximate e.s.d.) = 76.47 (2)

* 0.0000 (0.0000) O4 * 0.0000 (0.0000) C11 * 0.0000 (0.0000) C12 - 2.4600 (0.0045) N1 - 1.1646 (0.0064) C2

Rms deviation of fitted atoms = 0.0000

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.5667 (4)0.22403 (18)0.98584 (13)0.0491 (6)
O20.5280 (4)0.37524 (18)0.90086 (15)0.0652 (7)
O30.2206 (3)0.18768 (18)0.71575 (12)0.0457 (5)
O40.9620 (3)0.1801 (2)0.86098 (13)0.0462 (5)
N10.5624 (3)0.24890 (18)0.74759 (14)0.0349 (5)
C10.5560 (5)0.2772 (3)0.90909 (18)0.0399 (7)
C20.5774 (4)0.1939 (2)0.83343 (15)0.0339 (6)
C30.3828 (4)0.2419 (2)0.69714 (16)0.0325 (6)
C40.4196 (4)0.3118 (2)0.61848 (16)0.0320 (6)
C50.2828 (5)0.3318 (2)0.54723 (17)0.0394 (7)
C60.3540 (6)0.4043 (3)0.48278 (19)0.0499 (9)
C70.5552 (6)0.4542 (2)0.48836 (18)0.0478 (8)
C80.6884 (5)0.4343 (2)0.55979 (19)0.0425 (8)
C90.6180 (4)0.3623 (2)0.62557 (17)0.0339 (6)
C100.7226 (4)0.3259 (2)0.71118 (18)0.0383 (7)
C110.7722 (4)0.1165 (2)0.84408 (16)0.0355 (7)
C120.7996 (6)0.0391 (2)0.76572 (18)0.0471 (8)
H10.542 (7)0.266 (3)1.027 (3)0.091 (14)*
H41.047 (6)0.181 (3)0.820 (2)0.083 (14)*
H20.45080.14550.83750.041*
H50.14900.29750.54330.047*
H60.26580.42030.43460.060*
H70.60070.50160.44330.057*
H80.82240.46840.56370.051*
H10A0.85830.28840.70030.046*
H10B0.74650.38880.75050.046*
H110.74600.06990.89640.043*
H12A0.92280.00770.77510.071*
H12B0.81980.08240.71270.071*
H12C0.67370.00660.75950.071*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0561 (14)0.0606 (14)0.0306 (11)0.0086 (11)0.0091 (11)0.0019 (10)
O20.091 (2)0.0475 (13)0.0569 (14)0.0125 (13)0.0100 (13)0.0000 (11)
O30.0331 (11)0.0667 (13)0.0372 (10)0.0122 (12)0.0003 (9)0.0037 (10)
O40.0330 (11)0.0746 (14)0.0309 (11)0.0032 (12)0.0020 (10)0.0073 (10)
N10.0261 (12)0.0471 (13)0.0313 (11)0.0073 (12)0.0022 (10)0.0094 (10)
C10.0313 (17)0.0486 (18)0.0400 (16)0.0024 (15)0.0047 (14)0.0020 (13)
C20.0321 (16)0.0435 (15)0.0261 (13)0.0043 (14)0.0031 (11)0.0069 (12)
C30.0276 (15)0.0430 (16)0.0269 (13)0.0026 (14)0.0042 (11)0.0039 (12)
C40.0337 (17)0.0359 (14)0.0265 (13)0.0040 (15)0.0012 (11)0.0025 (11)
C50.0367 (16)0.0482 (18)0.0333 (14)0.0002 (15)0.0005 (14)0.0069 (13)
C60.066 (2)0.054 (2)0.0292 (15)0.0130 (17)0.0045 (15)0.0001 (14)
C70.068 (2)0.0421 (17)0.0333 (15)0.0057 (18)0.0108 (17)0.0065 (13)
C80.0454 (19)0.0383 (17)0.0437 (17)0.0049 (14)0.0106 (15)0.0052 (13)
C90.0352 (16)0.0333 (14)0.0333 (14)0.0031 (13)0.0031 (13)0.0007 (12)
C100.0295 (15)0.0445 (16)0.0409 (14)0.0063 (15)0.0015 (14)0.0074 (13)
C110.0361 (17)0.0412 (16)0.0292 (14)0.0022 (14)0.0030 (12)0.0058 (12)
C120.051 (2)0.0486 (18)0.0422 (17)0.0009 (16)0.0075 (15)0.0005 (14)
Geometric parameters (Å, º) top
O1—C11.322 (3)C3—C41.469 (4)
O2—C11.193 (3)C4—C51.391 (4)
O3—C31.232 (3)C4—C91.379 (4)
O4—C111.427 (3)C5—C61.376 (4)
N1—C21.454 (3)C6—C71.389 (4)
N1—C31.354 (3)C7—C81.379 (4)
N1—C101.465 (3)C8—C91.384 (4)
C1—C21.520 (4)C9—C101.509 (4)
C2—C111.534 (4)C11—C121.511 (3)
C2—N1—C3121.6 (2)C3—C4—C9109.1 (2)
C2—N1—C10125.1 (2)C5—C4—C9122.2 (2)
C3—N1—C10113.0 (2)C4—C5—C6117.2 (3)
O1—C1—O2124.9 (3)C5—C6—C7121.2 (3)
O1—C1—C2109.7 (2)C6—C7—C8121.0 (3)
O2—C1—C2125.4 (3)C7—C8—C9118.5 (3)
N1—C2—C1111.4 (2)C4—C9—C8120.0 (3)
N1—C2—C11114.7 (2)C4—C9—C10109.0 (2)
C1—C2—C11112.7 (2)C8—C9—C10131.0 (3)
O3—C3—N1125.5 (2)N1—C10—C9102.0 (2)
O3—C3—C4127.7 (2)O4—C11—C2110.5 (2)
N1—C3—C4106.8 (2)O4—C11—C12111.9 (2)
C3—C4—C5128.7 (3)C2—C11—C12112.2 (2)
C3—N1—C2—C1104.5 (3)C4—C5—C6—C70.8 (4)
C10—N1—C2—C168.3 (3)C5—C6—C7—C81.4 (4)
C3—N1—C2—C11125.9 (3)C6—C7—C8—C90.7 (4)
C10—N1—C2—C1161.3 (3)C5—C4—C9—C81.0 (4)
O2—C1—C2—N10.8 (4)C3—C4—C9—C8179.0 (2)
O1—C1—C2—N1178.9 (2)C5—C4—C9—C10178.4 (2)
O2—C1—C2—C11131.4 (3)C3—C4—C9—C100.4 (3)
O1—C1—C2—C1150.5 (3)C7—C8—C9—C40.4 (4)
C2—N1—C3—O32.3 (4)C7—C8—C9—C10178.7 (3)
C10—N1—C3—O3175.9 (3)C3—N1—C10—C92.9 (3)
C2—N1—C3—C4176.8 (2)C2—N1—C10—C9176.3 (2)
C10—N1—C3—C43.2 (3)C4—C9—C10—N11.4 (3)
O3—C3—C4—C9176.9 (3)C8—C9—C10—N1179.3 (3)
N1—C3—C4—C92.2 (3)N1—C2—C11—O478.1 (3)
O3—C3—C4—C50.9 (5)C1—C2—C11—O450.8 (3)
N1—C3—C4—C5180.0 (3)N1—C2—C11—C1247.5 (3)
C9—C4—C5—C60.3 (4)C1—C2—C11—C12176.4 (2)
C3—C4—C5—C6177.9 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O4i0.81 (4)1.87 (4)2.659 (3)162 (4)
O4—H4···O3ii0.82 (4)1.90 (4)2.718 (3)174 (4)
C10—H10A···O3ii0.972.573.513 (4)165
C5—H5···Cg2iii0.932.803.512 (3)134
C11—H11···Cg2iv0.982.773.573 (3)140
C12—H12C···Cg1iv0.962.843.672 (3)145
Symmetry codes: (i) x1/2, y+1/2, z+2; (ii) x+1, y, z; (iii) x1/2, y+1/2, z+1; (iv) x+1, y1/2, z+3/2.
(II) (2R/2S)-3-hydroxy-2-(1-oxoisoindolin-2-yl)butanoic acid top
Crystal data top
C12H13NO4Dx = 1.348 Mg m3
Mr = 235.23Melting point: 426 K
Monoclinic, P21/nMo Kα radiation, λ = 0.7107 Å
a = 5.9772 (7) ÅCell parameters from 25 reflections
b = 14.3906 (12) Åθ = 9.7–18.3°
c = 13.4926 (16) ŵ = 0.10 mm1
β = 93.131 (7)°T = 294 K
V = 1158.8 (2) Å3Block, colourless
Z = 40.39 × 0.35 × 0.21 mm
F(000) = 496
Data collection top
Enraf-Nonius CAD-4
diffractometer
Rint = 0.008
Radiation source: X-ray tubeθmax = 25.5°, θmin = 2.1°
Graphite monochromatorh = 77
ω/2θ scansk = 017
2242 measured reflectionsl = 016
2155 independent reflections3 standard reflections every 120 min
1623 reflections with I > 2σ(I) intensity decay: variation <0.5%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.034H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.086Calculated w = 1/[σ2(Fo2) + (0.0378P)2 + 0.2183P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max = 0.001
2155 reflectionsΔρmax = 0.16 e Å3
158 parametersΔρmin = 0.12 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 1997a), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.044 (3)
Crystal data top
C12H13NO4V = 1158.8 (2) Å3
Mr = 235.23Z = 4
Monoclinic, P21/nMo Kα radiation
a = 5.9772 (7) ŵ = 0.10 mm1
b = 14.3906 (12) ÅT = 294 K
c = 13.4926 (16) Å0.39 × 0.35 × 0.21 mm
β = 93.131 (7)°
Data collection top
Enraf-Nonius CAD-4
diffractometer
Rint = 0.008
2242 measured reflections3 standard reflections every 120 min
2155 independent reflections intensity decay: variation <0.5%
1623 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0340 restraints
wR(F2) = 0.086H atoms treated by a mixture of independent and constrained refinement
S = 1.05Δρmax = 0.16 e Å3
2155 reflectionsΔρmin = 0.12 e Å3
158 parameters
Special details top

Experimental. C—H···pi(arene) hydrogen bonds (with e.s.d.'s except fixed and riding H) ============================================================== D—H H···A D···A D—H···A Interaction ============================================================== 0.98 3.06 3.819 (2) 135.7 C11—H11···C4_$4 0.98 2.98 3.829 (2) 146.2 C11—H11···C5_$4 0.98 2.94 3.895 (2) 165.2 C11—H11···C6_$4 0.98 3.01 3.965 (2) 166.2 C11—H11···C7_$4 0.98 3.11 3.977 (2) 147.6 C11—H11···C8_$4 0.98 3.13 3.899 (2) 136.4 C11—H11···C9_$4

Geometry. Specific hydrogen bonds (with e.s.d.'s except fixed and riding H) ============================================================== D—H H···A D···A D—H···A Interaction ============================================================== 0.82 1.82 2.6355 (16) 174.7 O1—H1···O2_$2 0.82 1.94 2.7423 (15) 165.6 O4—H4···O3_$3 0.98 3.06 3.819 (2) 135.7 C11—H11···C4_$4 0.98 2.98 3.829 (2) 146.2 C11—H11···C5_$4 0.98 2.94 3.895 (2) 165.2 C11—H11···C6_$4 0.98 3.01 3.965 (2) 166.2 C11—H11···C7_$4 0.98 3.11 3.977 (2) 147.6 C11—H11···C8_$4 0.98 3.13 3.899 (2) 136.4 C11—H11···C9_$4 0.97 2.48 3.3137 (19) 144.3 C10—H10B···O3_$5

Mean plane data ex-SHELXL97 for molecule (II) #############################################

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

-3.5887(0.0039)x + 4.5284(0.0118)y + 10.3473(0.0076)z = 3.3296(0.0061)

* -0.0029 (0.0004) O1 * -0.0033 (0.0005) O2 * 0.0087 (0.0013) C1 * -0.0024 (0.0004) C2 1.1561 (0.0024) C11 - 0.0322 (0.0025) N1

Rms deviation of fitted atoms = 0.0050

2.6601(0.0034)x + 8.7249(0.0072)y + 8.5511(0.0068)z = 8.3378(0.0016)

Angle to previous plane (with approximate e.s.d.) = 65.91 (5)

* 0.0001 (0.0010) C4 * -0.0022 (0.0011) C5 * 0.0021 (0.0012) C6 * 0.0002 (0.0012) C7 * -0.0024 (0.0011) C8 * 0.0022 (0.0010) C9 0.0531 (0.0024) N1 - 0.0474 (0.0027) O3

Rms deviation of fitted atoms = 0.0018

2.6745(0.0040)x + 8.9186(0.0077)y + 8.3566(0.0079)z = 8.3457(0.0012)

Angle to previous plane (with approximate e.s.d.) = 1.13 (11)

* 0.0168 (0.0009) N1 * -0.0159 (0.0008) C3 * 0.0085 (0.0009) C4 * 0.0008 (0.0009) C9 * -0.0103 (0.0008) C10 - 0.0610 (0.0022) O3 - 1.2530 (0.0027) C1 0.0308 (0.0023) C2

Rms deviation of fitted atoms = 0.0120

-3.5887(0.0039)x + 4.5284(0.0118)y + 10.3473(0.0076)z = 3.3296(0.0061)

Angle to previous plane (with approximate e.s.d.) = 66.40 (6)

* -0.0029 (0.0004) O1 * -0.0033 (0.0005) O2 * 0.0087 (0.0013) C1 * -0.0024 (0.0004) C2 1.1561 (0.0024) C11 - 0.0322 (0.0025) N1

Rms deviation of fitted atoms = 0.0050

1.1393(0.0054)x - 5.4892(0.0277)y + 12.0457(0.0126)z = 7.5545(0.0132)

Angle to previous plane (with approximate e.s.d.) = 64.50 (8)

* 0.0000 (0.0000) O4 * 0.0000 (0.0000) C11 * 0.0000 (0.0000) C12 - 2.4914 (0.0021) N1 - 1.2374 (0.0035) C2

Rms deviation of fitted atoms = 0.0000

################################################################ (I) & (II) with DL-phenylalanine (III) and DL-meta-tyrosine (IV) derivatives: A carboxylic acid bond length and angle study ################################################################

(I) L-threonine derivative O1—C1 1.322 (3) O2—C1 1.193 (3) O3—C3 1.232 (3) O1—C1—O2 124.9 (3) O1—C1—C2 109.7 (2) O2—C1—C2 125.4 (3)

(II) DL-threonine derivative O1—C1 1.2961 (17) <<< O2—C1 1.2210 (18) <<< O3—C3 1.2350 (17) O1—C1—O2 124.05 (14) O1—C1—C2 113.29 (12) <<< O2—C1—C2 122.63 (13) <<<

DL-phenylalanine - CF1250 O1—C1 1.314 (2) O2—C1 1.194 (2) O3—C3 1.239 (2) O1—C1—O2 124.00 (18) O1—C1—C2 112.05 (16) O2—C1—C2 123.95 (18)

DL-meta-tyrosine - GD1055 O1—C1 1.328 (2) O2—C1 1.196 (2) O3—C3 1.236 (2) O1—C1—O2 124.3 (2) O1—C1—C2 110.17 (18) O2—C1—C2 125.55 (19)

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.7516 (2)0.03436 (8)0.56714 (10)0.0616 (4)
O20.5252 (2)0.10744 (8)0.45658 (9)0.0572 (4)
O31.06897 (17)0.26222 (9)0.36942 (8)0.0515 (3)
O40.64987 (17)0.23198 (9)0.67140 (7)0.0499 (3)
N10.77066 (19)0.26700 (8)0.46910 (8)0.0351 (3)
C10.6886 (3)0.10627 (10)0.51494 (10)0.0391 (4)
C20.8424 (2)0.18912 (10)0.53093 (10)0.0353 (3)
C30.8919 (2)0.29767 (10)0.39366 (10)0.0362 (3)
C40.7708 (2)0.37805 (10)0.34954 (10)0.0374 (3)
C50.8271 (3)0.43616 (12)0.27247 (11)0.0480 (4)
C60.6815 (3)0.50705 (12)0.24593 (12)0.0547 (5)
C70.4848 (3)0.51948 (11)0.29424 (13)0.0549 (5)
C80.4288 (3)0.46136 (11)0.37064 (12)0.0486 (4)
C90.5754 (2)0.39037 (10)0.39802 (10)0.0374 (3)
C100.5612 (2)0.31874 (10)0.47769 (11)0.0394 (4)
C110.8693 (2)0.21278 (10)0.64189 (10)0.0379 (3)
C121.0275 (3)0.29277 (12)0.66338 (13)0.0564 (5)
H10.66210.00810.55660.092*
H40.64960.23200.73220.075*
H20.99030.17030.51010.042*
H50.95870.42740.24000.058*
H60.71550.54720.19490.066*
H70.38870.56780.27490.066*
H80.29650.46980.40270.058*
H10A0.55450.34730.54260.047*
H10B0.43160.27890.46570.047*
H110.92670.15790.67800.046*
H12A1.03050.30740.73290.085*
H12B0.97740.34600.62550.085*
H12C1.17530.27580.64540.085*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0779 (9)0.0384 (6)0.0656 (8)0.0105 (6)0.0225 (7)0.0102 (6)
O20.0691 (8)0.0410 (7)0.0587 (7)0.0062 (6)0.0216 (6)0.0013 (5)
O30.0415 (6)0.0749 (8)0.0393 (6)0.0087 (6)0.0124 (5)0.0118 (5)
O40.0493 (6)0.0704 (8)0.0310 (6)0.0003 (6)0.0095 (5)0.0012 (5)
N10.0368 (6)0.0383 (7)0.0307 (6)0.0014 (5)0.0076 (5)0.0042 (5)
C10.0516 (9)0.0346 (8)0.0308 (7)0.0022 (7)0.0005 (7)0.0017 (6)
C20.0383 (8)0.0365 (8)0.0314 (7)0.0019 (6)0.0054 (6)0.0026 (6)
C30.0361 (8)0.0452 (9)0.0273 (7)0.0053 (7)0.0023 (6)0.0005 (6)
C40.0420 (8)0.0403 (8)0.0298 (7)0.0081 (6)0.0002 (6)0.0001 (6)
C50.0543 (9)0.0515 (10)0.0383 (8)0.0105 (8)0.0034 (7)0.0071 (8)
C60.0787 (12)0.0436 (9)0.0411 (9)0.0127 (9)0.0020 (9)0.0104 (7)
C70.0794 (12)0.0352 (9)0.0486 (10)0.0067 (8)0.0090 (9)0.0002 (7)
C80.0570 (10)0.0417 (9)0.0472 (9)0.0069 (8)0.0022 (8)0.0024 (7)
C90.0452 (8)0.0344 (8)0.0325 (7)0.0032 (6)0.0007 (6)0.0031 (6)
C100.0412 (8)0.0400 (8)0.0377 (8)0.0030 (6)0.0086 (6)0.0021 (7)
C110.0412 (8)0.0392 (8)0.0333 (7)0.0031 (7)0.0010 (6)0.0023 (6)
C120.0588 (11)0.0554 (11)0.0540 (10)0.0152 (9)0.0059 (8)0.0031 (9)
Geometric parameters (Å, º) top
O1—C11.2961 (17)C3—C41.473 (2)
O2—C11.2210 (18)C4—C51.390 (2)
O3—C31.2350 (17)C4—C91.381 (2)
O4—C111.4187 (17)C5—C61.375 (2)
N1—C21.4481 (18)C6—C71.387 (3)
N1—C31.3552 (17)C7—C81.383 (2)
N1—C101.4669 (18)C8—C91.383 (2)
C1—C21.514 (2)C9—C101.495 (2)
C2—C111.535 (2)C11—C121.508 (2)
C2—N1—C3122.08 (12)C3—C4—C9108.60 (12)
C2—N1—C10125.06 (11)C5—C4—C9121.50 (14)
C3—N1—C10112.83 (12)C4—C5—C6117.75 (15)
O1—C1—O2124.05 (14)C5—C6—C7120.92 (15)
O1—C1—C2113.29 (12)C6—C7—C8121.21 (16)
O2—C1—C2122.63 (13)C7—C8—C9118.07 (16)
N1—C2—C1111.67 (11)C4—C9—C8120.55 (14)
N1—C2—C11113.71 (12)C4—C9—C10109.57 (12)
C1—C2—C11110.14 (11)C8—C9—C10129.88 (14)
O3—C3—N1124.45 (14)N1—C10—C9102.16 (11)
O3—C3—C4128.80 (13)O4—C11—C2105.52 (11)
N1—C3—C4106.75 (12)O4—C11—C12112.15 (13)
C3—C4—C5129.90 (14)C2—C11—C12112.84 (12)
C3—N1—C2—C1112.29 (14)C4—C5—C6—C70.4 (2)
C10—N1—C2—C165.51 (17)C5—C6—C7—C80.2 (3)
C3—N1—C2—C11122.32 (14)C6—C7—C8—C90.3 (2)
C10—N1—C2—C1159.88 (18)C5—C4—C9—C80.2 (2)
O2—C1—C2—N10.2 (2)C3—C4—C9—C8179.67 (13)
O1—C1—C2—N1178.16 (13)C5—C4—C9—C10179.34 (13)
O2—C1—C2—C11127.18 (15)C3—C4—C9—C100.77 (16)
O1—C1—C2—C1154.49 (17)C7—C8—C9—C40.4 (2)
C2—N1—C3—O31.4 (2)C7—C8—C9—C10179.01 (15)
C10—N1—C3—O3176.68 (14)C3—N1—C10—C92.61 (15)
C2—N1—C3—C4178.81 (12)C2—N1—C10—C9179.40 (12)
C10—N1—C3—C43.14 (16)C4—C9—C10—N10.99 (15)
O3—C3—C4—C9177.43 (15)C8—C9—C10—N1178.52 (15)
N1—C3—C4—C92.39 (15)N1—C2—C11—O466.92 (15)
O3—C3—C4—C52.5 (3)C1—C2—C11—O459.28 (15)
N1—C3—C4—C5177.73 (14)N1—C2—C11—C1255.87 (17)
C9—C4—C5—C60.2 (2)C1—C2—C11—C12177.94 (13)
C3—C4—C5—C6179.93 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O2i0.821.822.6355 (16)175
O4—H4···O3ii0.821.942.7423 (15)166
C10—H10B···O3iii0.972.483.3140 (17)144
C11—H11···Cg2iv0.982.703.6440 (16)161
Symmetry codes: (i) x+1, y, z+1; (ii) x1/2, y+1/2, z+1/2; (iii) x1, y, z; (iv) x+1/2, y+1/2, z+1/2.

Experimental details

(I)(II)
Crystal data
Chemical formulaC12H13NO4C12H13NO4
Mr235.23235.23
Crystal system, space groupOrthorhombic, P212121Monoclinic, P21/n
Temperature (K)294294
a, b, c (Å)6.2209 (6), 11.9726 (13), 15.0705 (12)5.9772 (7), 14.3906 (12), 13.4926 (16)
α, β, γ (°)90, 90, 9090, 93.131 (7), 90
V3)1122.5 (2)1158.8 (2)
Z44
Radiation typeMo KαMo Kα
µ (mm1)0.110.10
Crystal size (mm)0.32 × 0.14 × 0.120.39 × 0.35 × 0.21
Data collection
DiffractometerEnraf-Nonius CAD-4
diffractometer
Enraf-Nonius CAD-4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
3932, 1967, 1441 2242, 2155, 1623
Rint0.0200.008
(sin θ/λ)max1)0.5950.606
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.040, 0.096, 1.01 0.034, 0.086, 1.05
No. of reflections19672155
No. of parameters163158
H-atom treatmentH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.16, 0.150.16, 0.12
Absolute structureFlack (1983)?
Absolute structure parameternot reliably determined?

Computer programs: CAD-4-PC Software (Enraf-Nonius, 1992), CAD-4-PC Software, NRCVAX96 (Gabe et al., 1989), SHELXS97 (Sheldrick, 1997b), NRCVAX96 and SHELXL97 (Sheldrick, 1997a), ORTEPIII (Burnett & Johnson, 1996), ORTEX (McArdle, 1995) and PLATON (Spek, 1998), NRCVAX96, SHELXL97 and PREP8 (Ferguson, 1998).

Selected geometric parameters (Å, º) for (I) top
O1—C11.322 (3)N1—C101.465 (3)
O2—C11.193 (3)C1—C21.520 (4)
O3—C31.232 (3)C2—C111.534 (4)
O4—C111.427 (3)C3—C41.469 (4)
N1—C21.454 (3)C9—C101.509 (4)
N1—C31.354 (3)C11—C121.511 (3)
C2—N1—C3121.6 (2)O3—C3—N1125.5 (2)
C2—N1—C10125.1 (2)O3—C3—C4127.7 (2)
C3—N1—C10113.0 (2)N1—C3—C4106.8 (2)
O1—C1—O2124.9 (3)C4—C9—C10109.0 (2)
O1—C1—C2109.7 (2)C8—C9—C10131.0 (3)
O2—C1—C2125.4 (3)N1—C10—C9102.0 (2)
N1—C2—C1111.4 (2)O4—C11—C2110.5 (2)
N1—C2—C11114.7 (2)O4—C11—C12111.9 (2)
C1—C2—C11112.7 (2)C2—C11—C12112.2 (2)
C3—N1—C2—C1104.5 (3)N1—C2—C11—O478.1 (3)
O2—C1—C2—N10.8 (4)C1—C2—C11—O450.8 (3)
Hydrogen-bond geometry (Å, º) for (I) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O4i0.81 (4)1.87 (4)2.659 (3)162 (4)
O4—H4···O3ii0.82 (4)1.90 (4)2.718 (3)174 (4)
C10—H10A···O3ii0.972.573.513 (4)165
C5—H5···Cg2iii0.932.803.512 (3)134
C11—H11···Cg2iv0.982.773.573 (3)140
C12—H12C···Cg1iv0.962.843.672 (3)145
Symmetry codes: (i) x1/2, y+1/2, z+2; (ii) x+1, y, z; (iii) x1/2, y+1/2, z+1; (iv) x+1, y1/2, z+3/2.
Selected geometric parameters (Å, º) for (II) top
O1—C11.2961 (17)N1—C101.4669 (18)
O2—C11.2210 (18)C1—C21.514 (2)
O3—C31.2350 (17)C2—C111.535 (2)
O4—C111.4187 (17)C3—C41.473 (2)
N1—C21.4481 (18)C9—C101.495 (2)
N1—C31.3552 (17)C11—C121.508 (2)
C2—N1—C3122.08 (12)O3—C3—N1124.45 (14)
C2—N1—C10125.06 (11)O3—C3—C4128.80 (13)
C3—N1—C10112.83 (12)N1—C3—C4106.75 (12)
O1—C1—O2124.05 (14)C4—C9—C10109.57 (12)
O1—C1—C2113.29 (12)C8—C9—C10129.88 (14)
O2—C1—C2122.63 (13)N1—C10—C9102.16 (11)
N1—C2—C1111.67 (11)O4—C11—C2105.52 (11)
N1—C2—C11113.71 (12)O4—C11—C12112.15 (13)
C1—C2—C11110.14 (11)C2—C11—C12112.84 (12)
C3—N1—C2—C1112.29 (14)N1—C2—C11—O466.92 (15)
O1—C1—C2—N1178.16 (13)C1—C2—C11—O459.28 (15)
Hydrogen-bond geometry (Å, º) for (II) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O2i0.821.822.6355 (16)175
O4—H4···O3ii0.821.942.7423 (15)166
C10—H10B···O3iii0.972.483.3140 (17)144
C11—H11···Cg2iv0.982.703.6440 (16)161
Symmetry codes: (i) x+1, y, z+1; (ii) x1/2, y+1/2, z+1/2; (iii) x1, y, z; (iv) x+1/2, y+1/2, z+1/2.
 

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