Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270102020814/jz1532sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270102020814/jz1532Isup2.hkl |
CCDC reference: 204045
The title compound was synthesized by dropwise addition of a diethyl ether solution of chloroacetyl chloride (0.88 mol in 180 ml) to an equimolecular aqueous solution of β-alanine (0.8 mol in 200 ml) and sodium hydroxide. The reaction mixture was kept at a temperature of 268 K and a pH close to 11–12 by gradual addition of concentrated NaOH solution to neutralize the hydrochloric acid produced during the condensation. After 16 h of stirring at room temperature, the solution was evaporated under reduced pressure. The solid product was extracted with hot acetone, and the resulting solution was evaporated again. Finally, a white solid was obtained and recrystallized from 2-propanol to give colorless prismatic crystals (yield 55%, m.p. 365 K). 1H NMR (CDCl3/TFA, TMS, internal reference): δ 7.6 (s, 1H, COOH), 7.3 (m, 1H, NH), 4.2 (s, 2H, ClCH2CO), 3.7 (m, 2H, NHCH2), 2.8 (t, 2H, CH2COO).
The two H atoms involved in hydrogen bonds were located in the difference Fourier maps and refined isotropically. The reamaining H atoms were placed in calculated positions and refined riding on their attached C atoms (C—H = 0.97 Å), with Uiso values of 1.2 times the Ueq values of the parent atoms.
Data collection: CAD-4 Software (Kiers, 1994); cell refinement: CAD-4 Software (Kiers, 1994); data reduction: local program; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976) and CERIUS2 (Accelrys Molecular Simulations, 2002); software used to prepare material for publication: UNIX.
C5H8ClNO3 | F(000) = 688 |
Mr = 165.57 | Dx = 1.450 Mg m−3 |
Monoclinic, C2/c | Melting point: 365 K |
Hall symbol: -C 2yc | Mo Kα radiation, λ = 0.71073 Å |
a = 14.41 (2) Å | Cell parameters from 25 reflections |
b = 7.282 (6) Å | θ = 12–21° |
c = 14.672 (2) Å | µ = 0.45 mm−1 |
β = 99.96 (6)° | T = 293 K |
V = 1516 (2) Å3 | Prism, colourless |
Z = 8 | 0.2 × 0.1 × 0.1 mm |
Enraf-Nonius CAD4 diffractometer | Rint = 0.020 |
Radiation source: fine-focus sealed tube | θmax = 26.4°, θmin = 2.8° |
Graphite monochromator | h = −18→17 |
ω/2θ scans | k = 0→9 |
1632 measured reflections | l = 0→18 |
1550 independent reflections | 1 standard reflections every 120 min |
951 reflections with I > 2σ(I) | intensity decay: none |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.052 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.145 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.03 | w = 1/[σ2(Fo2) + (0.0647P)2 + 1.1856P] where P = (Fo2 + 2Fc2)/3 |
1550 reflections | (Δ/σ)max < 0.001 |
99 parameters | Δρmax = 0.32 e Å−3 |
0 restraints | Δρmin = −0.24 e Å−3 |
C5H8ClNO3 | V = 1516 (2) Å3 |
Mr = 165.57 | Z = 8 |
Monoclinic, C2/c | Mo Kα radiation |
a = 14.41 (2) Å | µ = 0.45 mm−1 |
b = 7.282 (6) Å | T = 293 K |
c = 14.672 (2) Å | 0.2 × 0.1 × 0.1 mm |
β = 99.96 (6)° |
Enraf-Nonius CAD4 diffractometer | Rint = 0.020 |
1632 measured reflections | 1 standard reflections every 120 min |
1550 independent reflections | intensity decay: none |
951 reflections with I > 2σ(I) |
R[F2 > 2σ(F2)] = 0.052 | 0 restraints |
wR(F2) = 0.145 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.03 | Δρmax = 0.32 e Å−3 |
1550 reflections | Δρmin = −0.24 e Å−3 |
99 parameters |
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. Mean-plane data from final SHELXL refinement run: Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane) − 1.7795 (0.0265) x + 7.1748 (0.0117) y − 1.3961 (0.0268) z = 3.2938 (0.0203) * 0.0038 (0.0026) C5 * −0.0012 (0.0008) O3 * −0.0015 (0.0010) O2 * −0.0011 (0.0008) C4 Rms deviation of fitted atoms = 0.0022 − 9.4262 (0.0916) x + 2.8760 (0.0094) y + 10.9834 (0.0752) z = 0.3659 (0.0931) Angle to previous plane (with approximate e.s.d.) = 66.82 (0.17) * 0.0129 (0.0102) N1 * 0.0010 (0.0030) C2 * −0.0006 (0.0060) C3 * −0.0045 (0.0090) O1 * 0.0013 (0.0066) C1 * −0.0101 (0.0150) H1 Rms deviation of fitted atoms = 0.0070 − 9.3635 (9.9990) x + 2.8780 (9.9990) y + 11.0333 (9.9990) z = 0.4304 (1.8793) Angle to previous plane (with approximate e.s.d.) = 0.35 (99.99) * 0.0062 (0.0246) N1 * −0.0003 (0.0031) C2 * −0.0045 (0.0217) C3 * 0.0016 (0.0084) O1 * −0.0030 (0.0157) C1 Rms deviation of fitted atoms = 0.0038 |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
Cl1 | 0.47761 (7) | 0.18691 (14) | 0.38496 (8) | 0.0835 (4) | |
O1 | 0.70041 (14) | 0.4456 (3) | 0.51733 (14) | 0.0515 (6) | |
O3 | 0.75081 (16) | 0.6815 (4) | 0.18703 (18) | 0.0648 (7) | |
H3 | 0.732 (3) | 0.660 (6) | 0.130 (3) | 0.092 (15)* | |
N1 | 0.58815 (18) | 0.5350 (4) | 0.39916 (17) | 0.0465 (6) | |
H1 | 0.539 (2) | 0.511 (4) | 0.362 (2) | 0.056 (10)* | |
O2 | 0.60000 (15) | 0.6462 (4) | 0.19818 (15) | 0.0732 (8) | |
C5 | 0.6811 (2) | 0.6742 (4) | 0.2345 (2) | 0.0483 (7) | |
C2 | 0.6258 (2) | 0.4150 (4) | 0.4618 (2) | 0.0429 (7) | |
C4 | 0.7130 (2) | 0.7011 (4) | 0.3358 (2) | 0.0504 (8) | |
H4A | 0.7496 | 0.8133 | 0.3455 | 0.060* | |
H4B | 0.7540 | 0.6001 | 0.3597 | 0.060* | |
C3 | 0.6329 (2) | 0.7122 (4) | 0.3900 (2) | 0.0511 (8) | |
H3A | 0.6568 | 0.7603 | 0.4512 | 0.061* | |
H3B | 0.5860 | 0.7975 | 0.3593 | 0.061* | |
C1 | 0.5785 (2) | 0.2325 (4) | 0.4690 (2) | 0.0543 (8) | |
H1A | 0.5606 | 0.2245 | 0.5297 | 0.065* | |
H1B | 0.6243 | 0.1363 | 0.4654 | 0.065* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0649 (6) | 0.0744 (7) | 0.1028 (8) | −0.0246 (5) | −0.0094 (5) | −0.0005 (6) |
O1 | 0.0425 (11) | 0.0610 (14) | 0.0483 (11) | −0.0028 (10) | 0.0000 (9) | 0.0037 (11) |
O3 | 0.0488 (14) | 0.0912 (19) | 0.0563 (15) | −0.0176 (12) | 0.0142 (12) | −0.0128 (14) |
N1 | 0.0407 (14) | 0.0492 (16) | 0.0471 (14) | −0.0002 (12) | 0.0006 (12) | 0.0013 (13) |
O2 | 0.0422 (13) | 0.120 (2) | 0.0554 (14) | −0.0148 (13) | 0.0016 (11) | −0.0092 (15) |
C5 | 0.0459 (17) | 0.0446 (17) | 0.0535 (17) | −0.0082 (14) | 0.0060 (15) | −0.0027 (15) |
C2 | 0.0367 (15) | 0.0477 (18) | 0.0463 (16) | 0.0012 (12) | 0.0128 (13) | −0.0039 (14) |
C4 | 0.0495 (17) | 0.0493 (18) | 0.0495 (17) | −0.0138 (14) | 0.0004 (14) | −0.0022 (15) |
C3 | 0.0589 (19) | 0.0426 (18) | 0.0496 (17) | 0.0017 (15) | 0.0036 (15) | −0.0047 (15) |
C1 | 0.0467 (17) | 0.0542 (19) | 0.0624 (19) | −0.0047 (15) | 0.0106 (15) | 0.0016 (16) |
Cl1—C1 | 1.768 (4) | C2—C1 | 1.506 (4) |
O1—C2 | 1.251 (4) | C4—C3 | 1.512 (5) |
O3—C5 | 1.320 (4) | C4—H4A | 0.9700 |
O3—H3 | 0.84 (4) | C4—H4B | 0.9700 |
N1—C2 | 1.316 (4) | C3—H3A | 0.9700 |
N1—C3 | 1.459 (4) | C3—H3B | 0.9700 |
N1—H1 | 0.83 (3) | C1—H1A | 0.9700 |
O2—C5 | 1.215 (4) | C1—H1B | 0.9700 |
C5—C4 | 1.491 (4) | ||
C5—O3—H3 | 112 (3) | C3—C4—H4B | 108.9 |
C2—N1—C3 | 121.1 (3) | H4A—C4—H4B | 107.7 |
C2—N1—H1 | 121 (2) | N1—C3—C4 | 113.0 (3) |
C3—N1—H1 | 118 (2) | N1—C3—H3A | 109.0 |
O2—C5—O3 | 122.5 (3) | C4—C3—H3A | 109.0 |
O2—C5—C4 | 124.6 (3) | N1—C3—H3B | 109.0 |
O3—C5—C4 | 112.9 (3) | C4—C3—H3B | 109.0 |
O1—C2—N1 | 122.7 (3) | H3A—C3—H3B | 107.8 |
O1—C2—C1 | 117.4 (3) | C2—C1—Cl1 | 116.4 (2) |
N1—C2—C1 | 119.9 (3) | C2—C1—H1A | 108.2 |
C5—C4—C3 | 113.5 (3) | Cl1—C1—H1A | 108.2 |
C5—C4—H4A | 108.9 | C2—C1—H1B | 108.2 |
C3—C4—H4A | 108.9 | Cl1—C1—H1B | 108.2 |
C5—C4—H4B | 108.9 | H1A—C1—H1B | 107.3 |
C3—N1—C2—O1 | 1.0 (4) | C2—N1—C3—C4 | 80.5 (3) |
C3—N1—C2—C1 | −179.4 (3) | C5—C4—C3—N1 | 73.1 (3) |
O2—C5—C4—C3 | −6.6 (5) | O1—C2—C1—Cl1 | −176.0 (2) |
O3—C5—C4—C3 | 174.2 (3) | N1—C2—C1—Cl1 | 4.4 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O1i | 0.84 (4) | 1.81 (4) | 2.638 (3) | 165 (4) |
N1—H1···O2ii | 0.83 (3) | 2.27 (3) | 2.951 (5) | 139 (3) |
N1—H1···Cl1 | 0.83 (3) | 2.56 (3) | 2.982 (4) | 112 (3) |
C1—H1A···O2iii | 0.97 | 2.61 | 3.438 (4) | 143 |
C1—H1B···O1iv | 0.97 | 2.57 | 3.414 (6) | 146 |
C4—H4A···O1v | 0.97 | 2.67 | 3.448 (4) | 137 |
Symmetry codes: (i) x, −y+1, z−1/2; (ii) −x+1, y, −z+1/2; (iii) x, −y+1, z+1/2; (iv) −x+3/2, −y+1/2, −z+1; (v) −x+3/2, −y+3/2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C5H8ClNO3 |
Mr | 165.57 |
Crystal system, space group | Monoclinic, C2/c |
Temperature (K) | 293 |
a, b, c (Å) | 14.41 (2), 7.282 (6), 14.672 (2) |
β (°) | 99.96 (6) |
V (Å3) | 1516 (2) |
Z | 8 |
Radiation type | Mo Kα |
µ (mm−1) | 0.45 |
Crystal size (mm) | 0.2 × 0.1 × 0.1 |
Data collection | |
Diffractometer | Enraf-Nonius CAD4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 1632, 1550, 951 |
Rint | 0.020 |
(sin θ/λ)max (Å−1) | 0.625 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.052, 0.145, 1.03 |
No. of reflections | 1550 |
No. of parameters | 99 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.32, −0.24 |
Computer programs: CAD-4 Software (Kiers, 1994), local program, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEPII (Johnson, 1976) and CERIUS2 (Accelrys Molecular Simulations, 2002), UNIX.
C3—N1—C2—C1 | −179.4 (3) | C5—C4—C3—N1 | 73.1 (3) |
O3—C5—C4—C3 | 174.2 (3) | N1—C2—C1—Cl1 | 4.4 (4) |
C2—N1—C3—C4 | 80.5 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O1i | 0.84 (4) | 1.81 (4) | 2.638 (3) | 165 (4) |
N1—H1···O2ii | 0.83 (3) | 2.27 (3) | 2.951 (5) | 139 (3) |
N1—H1···Cl1 | 0.83 (3) | 2.56 (3) | 2.982 (4) | 112 (3) |
C1—H1A···O2iii | 0.97 | 2.61 | 3.438 (4) | 143 |
C1—H1B···O1iv | 0.97 | 2.57 | 3.414 (6) | 146 |
C4—H4A···O1v | 0.97 | 2.67 | 3.448 (4) | 137 |
Symmetry codes: (i) x, −y+1, z−1/2; (ii) −x+1, y, −z+1/2; (iii) x, −y+1, z+1/2; (iv) −x+3/2, −y+1/2, −z+1; (v) −x+3/2, −y+3/2, −z+1. |
Polyesters constitute an important group of biodegradable polymers because of their potentially hydrolyzable ester bond. Furthermore, they have specialized applications in the field of medical technology, since both the polymers and their degradation products are usually non-toxic; an example is the use of polyglycolide, polylactide and poly(glycolide-co-lactide) as surgical sutures (Vert et al., 1995). Nowadays, considerable efforts are being focused on improving the synthesis of polyesters and obtaining related polymers with enhanced properties. In this way, poly(ester amide)s derived from glycolic acid and amino acids, such as glycine or β-alanine, appear a viable alternative because of the properties afforded by the establishment of strong intermolecular hydrogen bonds. A further possibility is the solid-state polycondensation of halogenated carboxylates, which is an interesting method for the preparation of polyglycolide (Herzberg & Epple, 2001) and its derivatives; the resulting polymers display novel properties (porous micromorphology). A molecular solid-state reaction relies on a suitable arrangement of the reactants in the crystal, and the study of the relevant crystal structures is therefore fundamental. In general, this kind of halogen derivative yields microcrystals and, consequently, few structures have been solved by single-crystal diffraction (Epple & Kirschnick, 1997). The title compound, (I), has been chosen as the precursor of salts that could be polymerized in the solid state to obtain the sequential poly(ester amide) derived from glycolic acid and β-alanine.
The molecule of (I) is shown in Fig. 1, whereas selected torsion angles and hydrogen-bond geometry are reported in Tables 1 and 2. Amide and ester groups are planar within experimental error, with an r.m.s. distance of the atoms from the best planes passing through them of 0.0022 and 0.0070 Å for the C4/C5/O2/O3 and C1/C2/O1/N1/H1/C3 planes, respectively. The packing is characterized by the establishment of a network of intermolecular hydrogen bonds involving amide—acid interactions between the H atoms of the NH and OH groups, and the CO group of the acid and amide groups, respectively. N—H···O═C interactions are established between molecules related by a binary axis and, consequently, with an antiparallel arrangement, whereas O—H···O═C interactions link molecules related by the c-glide plane and, therefore, with opposite signs for equivalent torsion angles. These hydrogen bonds combine to produce a ribbon structure, as depicted in Fig. 2, where a row of molecules linked by O—H···O═C interactions is aligned parallel to the z axis. In addition, weak C—H···O═C intermolecular hydrogen bonds were also detected (Table 2).
The molecular conformation of (I) shows interesting features, concerning the chloroacetyl unit and the β-alanine residue, which is a constituent of some natural peptides (Bershon & Inhat, 1970; Bullough et al., 1982). Accordingly, a number of small model peptides containing this residue have been investigated by X-ray crystallography (Banerjee & Balaram, 1997). Furthermore, conformational preferences of the dipeptide N-acetyl-β-alanineamide (Wu & Wang, 1998) have recently been studied using quantum mechanical gas-phase calculations. The results indicate that folded conformations, such as ggt, are energetically stabilized by an intramolecular six-membered hydrogen-bonded ring. This conformation is found in (I) and also in other compounds (Maji et al., 2001) where intermolecular hydrogen bonds could be established in the solid state. However, the torsion angles of (I) deviate slightly from the theoretical values [e.g. 80.5 (3)° instead of 60° for the C(═O)—NH—CH2—CH2 angle] and, thus, the intramolecular hydrogen bond is weakened to such an extent that it effectively loses its identity [H1—O2 = 2.87 (3) Å, N1—O2 = 3.091 (3) Å and N1—H1—O2 = 98 (2)°]. This may be due to the competition of two hydrogen-bond acceptors (Cl1 and O2) for forming an intramolecular hydrogen bond with N1—H1; atom O2 is involved in an intermolecular hydrogen bond with N1—H1 (Table 2). A survey of the Cambridge Structural Database (Allen, 2002) shows 36 crystal structures containing a total of 55 X—CONHCH2CH2CO—X units, which demonstrate the preferences for a folded conformation. Thus, the torsion angles ϕ [C(═O)—NH—CH2—CH2], ξ [NH—CH2—CH2—C(═O)] and ψ [CH2—CH2—C(═O)—O] preferentially adopt skew-gauche (45–34%), gauche (52%) and trans (43%) conformations, respectively.
Finally, it is noteworthy that the Cl—CH2—C(═O)—NH torsion angle has a cis conformation, in agreement with the results obtained for other related structures, such as chloroacetylglycylglycine (Rao & Mallikarjunan, 1973) and 2-chloroacetamide (Kalyanaraman et al., 1978). This conformation is clearly stabilized by an N—H···Cl intramolecular hydrogen bond (Table 2).