Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270110023334/sk3374sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270110023334/sk3374Isup2.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270110023334/sk3374IIsup3.hkl |
CCDC references: 790637; 790638
The title compounds could be easily prepared by nucleophilic vinylic substitution of equimolar amounts of 2-ethoxymethylene-3-oxobutanenitrile or 5-ethoxymethylene-4,6-dioxo-2,2-dimethyl-1,3-dioxane with 3-fluoroaniline in boiling ethanol (Leya et al., 1999).
For (I), a rotational disorder of the phenyl ring has been resolved on F3/F5 positions with the distance C—F restrained to a common value (refined) with an s.u. of 0.02 Å allowed. Aromatic H atoms were refined isotropically with Uĩso(H) = 1.2Ueq(C) and their positions were constrained to ideal geometry using an appropriate riding model, with N—H = 0.88 Å and C—H = 0.95 Å. For methyl groups, C—C—H angles (109.5°) were kept fixed, while the torsion angle was allowed to refine with the starting positions based on the circular Fourier synthesis averaged using the local threefold axis with Uĩso(H)= 1.5Ueq(C) and C—H = 0.98 Å. In (I), the methyl group is also disordered and has been refined with two components with 50% occupancy, rotated 60° relative to each other. Molecular calculations were done at the B3LYP/6–31+G** level of theory using GAUSSIAN98 (Frisch et al., 1998). Natural bond orbital (Foster & Weinhold, 1980) calculations were done using the NBO 3.1 version (Glendening et al., 1993) of the program included in the GAUSSIAN package.
The heteroarylaminoethylene type of compounds substituted with fluorine are not only excellent precursors for the synthesis of biologically active 4-quinolones, but they are also biologically active themselves as they show e.g. photobleaching activity towards cells of Nicotiana tabacum, and fungicides [fungicidal?], germicides [germicidal?] or herbicides [herbicidal?] [properties?]. The title compounds were synthesized within the framework of our continuous study (Langer et al., 2006, 2009; Smrčok et al., 2007) of the structure and properties of potential precursors of fluoroquinolones, knowledge of which has proved essential in reaction pathway considerations and planning.
Perspective drawings of the title molecules are shown in Fig.1 for (I) and in Fig.2 for (II). The structure of (I) shows a disorder of the phenyl ring (rotation by 180°) with occupancy of 0.890 (1) for the main component and the methyl group at C10 has been refined with occupancy of 50% for two orientations with 60° relative to each other. Considering the calculated dipole moments for the molecules of (I) and (II) (4.5 and 2.3 D), it can be assumed that the main packing force in both structures is electrostatic. The basic building unit in both structures comprises molecules joined pairwise via different hydrogen bonds and the constituting [resulting?] pairs are cross-linked to form three-dimensional hydrogen-bonded networks. The fundamental structural motif in the structure of (I) is pairs of molecules arranged in an antiparallel fashion which enables C—H···N≡C interactions (Fig. 3). Every N atom is an acceptor of two hydrogen bonds of two slightly different lengths (Table 1). The pairs of molecules are cross-linked by two weak C—H···O hydrogen bonds aiming at the O1 oxygen atom, which is also involved in the very bent intramolecular N1—H1···O1 hydrogen bond (Table 1). This arrangement can be described as a ribbon of molecules running approximately parallel to [101]. The pair of molecules in the structure of (II) is formed by the intermolecular bifurcated C2—H2···O1iv/O2iv and the combined inter- and intramolecular N1—H1···O1/O1iv hydrogen bonds (Fig. 4). These basic pairs of molecules form sheets through the C5—H5···O4v hydrogen bond. Although the arrangement of neighboring sheets is dictated mainly by electrostatic forces they also connected though C12—H12B···Ovi hydrogen bonding.
In both structures F atoms appear in such positions that they could form weak C—F···H—C interactions (Howard et al., 1996; Dunitz & Taylor, 1997) with the H atoms of the two neighbouring methyl groups, i.e. two H10A atoms in the structure of (I), and the H12C and H13C atoms in the structure of (II). The H···F separations, 2.59/2.80 Å in (I) and 2.63/2.71 Å (II), are well within the limits found for this type of non-bonded contact (Shimoni & Glusker, 1994).
NBO (natural bond orbitals) analysis (Foster & Weinhold, 1980) carried out for the isolated molecules reveals a general delocalization pattern, which can be characterized (i) by the delocalization of the lone pair of the N atom into the C═C antibonding orbital resulting in the lowering of the bond order of this bond and in the increase of the bond order of the N1—C7 bond, and (ii) by shifting of the electrons from the C═O double bonds towards the pπ orbital of the O atoms resulting in the relatively large partial negative charge on O1 [NBO charges are -0.621 |e| in (I) and -0.622 |e| in (II)] and also in a decrease of its bond order (Tables 2 and 3). This shift is further enhanced by formation of an intramolecular O1···H1—N1 hydrogen bond. All these changes are qualitatively described by a superposition of resonance structures, depicted in Fig. 5. The most obvious geometric consequences of such electron delocalizations are shortening of the formally single N1—C7 bond and also lengthening of the formally double C7═C8 bond, reflected in the decrease of the bond order (Tables 2 and 3). Another consequence of electron redistribution is structural rigidity of the N1—C7—C8-(C9—O1)(C11—N2) moiety in (I), which is further enhanced by formation of an intramolecular N1—H1···O1 hydrogen bond.
The additional characteristic feature of the C1—N1—C7—C8 fragment is increased values of the skeletal angles, namely C1—N1—C7 [125.15 (14)° in (I), 125.6 (2)° in (II))] and N1—C7—C8 [124.79 (15)° in (I) and 127.4 (3)° in (II)] relative to the expected ideal value of 120°. The main reason is the increased s content in the hybrid orbitals on the N1 and C7 atoms as a consequence of the shortening of the N1—C7 bond. This increase in s character in turn brings about an increase in the p character in two other formally sp2 hybrids and thus lowers the angle between them (Bent, 1961; Langer et al., 2009).
The phenyl ring connected to the aminomethylene group is, in both structures, only slightly rotated from the plane of the N1—C7—C8—C9—C11 atoms, the torsion angle C7—N1—C1—C6 being -1.6 (2)° in (I) and -2.7 (4)° in (II). Full optimizations of the molecular geometry in vacuum, however, give remarkably larger torsion angles, ~13° (I) and ~11° (II), but a closer inspection of the torsion potential around the C1—N1 bond reveals that it is, in both cases, very flat. Its flatness can be documented by the fact that the strictly planar structure of (I) has a total energy of only 0.06 kJ mol-1 higher than the minimum and the calculated harmonic torsion frequency is only 14 cm-1. Such flatness of the torsion potentials is a compromise between the two competing interactions – on the one hand, the repulsion of the H1—H2 and the H6—H7 H atoms tending to rotate the ring from the planar position and, on the other hand, delocalization of a lone pair of the N atom into the phenyl ring, stabilizing the planar arrangement.
An interesting feature of this torsion potential is the low barrier for ~180° rotation of the substituted phenyl ring, leading to conformations (Ia) and (IIa). According to the molecular calculation in vacuum, these conformations are even slightly more stable than the molecules of (I) and (II), i.e. 0.6 and 0.4 kJ mol-1, respectively. In (I), this conformation (Ia) is present as a minor component with an occupancy of 0.110 (1). The rotation barriers separating these conformers are also rather small, 14.7 and 15.0 kJ mol-1, and are further reduced by a polar medium. For instance, our polarizable continuum model (PCM; Miertuš et al., 1981; Foresman et al., 1996) calculation revealed that in water the barrier further reduces to 10.2 and 11.7 kJ mol-1, respectively. The preference of the (I) and (II) over (Ia) and (IIa) in the real structures is thus apparently a result of the packing forces in the crystals.
For related literature, see: Bent (1961); Dunitz & Taylor (1997); Foresman et al. (1996); Foster & Weinhold (1980); Frisch et al. (1998); Glendening et al. (1993); Howard et al. (1996); Langer et al. (2006, 2009); Leya et al. (1999); Miertuš et al. (1981); Shimoni & Glusker (1994); Smrčok et al. (2007).
For both compounds, data collection: SMART (Bruker, 2003); cell refinement: SAINT (Bruker, 2003); data reduction: SAINT (Bruker, 2003), SADABS (Sheldrick, 2003); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2009); software used to prepare material for publication: PLATON (Spek, 2009).
C11H9FN2O | F(000) = 424 |
Mr = 204.20 | Dx = 1.439 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2yn | Cell parameters from 2408 reflections |
a = 13.907 (2) Å | θ = 2.5–29.1° |
b = 5.0357 (8) Å | µ = 0.11 mm−1 |
c = 14.233 (2) Å | T = 153 K |
β = 108.946 (4)° | Needle, colourless |
V = 942.8 (3) Å3 | 0.49 × 0.12 × 0.08 mm |
Z = 4 |
Siemens CCD area-detector diffractometer | 2554 independent reflections |
Radiation source: fine-focus sealed tube | 1650 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.072 |
ω scans | θmax = 29.3°, θmin = 2.5° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | h = −19→19 |
Tmin = 0.949, Tmax = 0.991 | k = −6→6 |
13411 measured reflections | l = −19→19 |
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)] = 0.047 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.128 | H-atom parameters constrained |
S = 1.01 | w = 1/[σ2(Fo2) + (0.0565P)2 + 0.1626P] where P = (Fo2 + 2Fc2)/3 |
2554 reflections | (Δ/σ)max = 0.001 |
148 parameters | Δρmax = 0.25 e Å−3 |
2 restraints | Δρmin = −0.20 e Å−3 |
C11H9FN2O | V = 942.8 (3) Å3 |
Mr = 204.20 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 13.907 (2) Å | µ = 0.11 mm−1 |
b = 5.0357 (8) Å | T = 153 K |
c = 14.233 (2) Å | 0.49 × 0.12 × 0.08 mm |
β = 108.946 (4)° |
Siemens CCD area-detector diffractometer | 2554 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | 1650 reflections with I > 2σ(I) |
Tmin = 0.949, Tmax = 0.991 | Rint = 0.072 |
13411 measured reflections |
R[F2 > 2σ(F2)] = 0.047 | 2 restraints |
wR(F2) = 0.128 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.25 e Å−3 |
2554 reflections | Δρmin = −0.20 e Å−3 |
148 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. |
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 | Occ. (<1) | |
F3 | 0.93705 (9) | 1.6802 (2) | 0.54075 (9) | 0.0395 (4) | 0.890 (3) |
F5 | 0.7392 (9) | 1.410 (2) | 0.7260 (7) | 0.052 (4) | 0.110 (3) |
O1 | 0.68220 (9) | 0.7314 (2) | 0.24770 (9) | 0.0314 (3) | |
N1 | 0.70183 (10) | 0.9774 (2) | 0.42203 (10) | 0.0244 (3) | |
H1 | 0.7223 | 0.9751 | 0.3696 | 0.029* | |
N2 | 0.46035 (11) | 0.2881 (3) | 0.38393 (11) | 0.0375 (4) | |
C1 | 0.74737 (12) | 1.1674 (3) | 0.49746 (11) | 0.0232 (3) | |
C2 | 0.82132 (12) | 1.3321 (3) | 0.48250 (12) | 0.0256 (3) | |
H2 | 0.8410 | 1.3162 | 0.4248 | 0.031* | |
C3 | 0.86501 (12) | 1.5190 (3) | 0.55425 (12) | 0.0278 (4) | |
H3 | 0.9156 | 1.6323 | 0.5446 | 0.033* | 0.110 (3) |
C4 | 0.83942 (13) | 1.5509 (3) | 0.63927 (12) | 0.0291 (4) | |
H4 | 0.8712 | 1.6820 | 0.6873 | 0.035* | |
C5 | 0.76566 (14) | 1.3845 (3) | 0.65195 (13) | 0.0318 (4) | |
H5 | 0.7464 | 1.4021 | 0.7099 | 0.038* | 0.890 (3) |
C6 | 0.71898 (13) | 1.1923 (3) | 0.58215 (12) | 0.0290 (4) | |
H6 | 0.6684 | 1.0795 | 0.5921 | 0.035* | |
C7 | 0.63120 (12) | 0.8040 (3) | 0.42450 (12) | 0.0252 (3) | |
H7 | 0.6079 | 0.8087 | 0.4802 | 0.030* | |
C8 | 0.58877 (11) | 0.6159 (3) | 0.35173 (11) | 0.0233 (3) | |
C9 | 0.61772 (12) | 0.5840 (3) | 0.26291 (12) | 0.0245 (3) | |
C10 | 0.56819 (14) | 0.3686 (3) | 0.19082 (12) | 0.0314 (4) | |
H10A | 0.5677 | 0.4188 | 0.1241 | 0.047* | 0.50 |
H10B | 0.4982 | 0.3433 | 0.1904 | 0.047* | 0.50 |
H10C | 0.6063 | 0.2028 | 0.2108 | 0.047* | 0.50 |
H10D | 0.5471 | 0.2245 | 0.2261 | 0.047* | 0.50 |
H10E | 0.6166 | 0.3000 | 0.1598 | 0.047* | 0.50 |
H10F | 0.5085 | 0.4405 | 0.1394 | 0.047* | 0.50 |
C11 | 0.51691 (13) | 0.4372 (3) | 0.36984 (12) | 0.0268 (4) |
U11 | U22 | U33 | U12 | U13 | U23 | |
F3 | 0.0417 (7) | 0.0370 (6) | 0.0458 (8) | −0.0159 (5) | 0.0225 (6) | −0.0090 (5) |
F5 | 0.082 (9) | 0.045 (6) | 0.033 (6) | −0.003 (5) | 0.026 (6) | −0.009 (4) |
O1 | 0.0384 (7) | 0.0270 (5) | 0.0320 (6) | −0.0064 (5) | 0.0159 (5) | −0.0015 (5) |
N1 | 0.0299 (7) | 0.0215 (6) | 0.0226 (7) | 0.0007 (5) | 0.0096 (6) | −0.0025 (5) |
N2 | 0.0389 (9) | 0.0370 (8) | 0.0410 (9) | −0.0077 (7) | 0.0191 (8) | −0.0064 (7) |
C1 | 0.0261 (8) | 0.0175 (6) | 0.0231 (8) | 0.0037 (6) | 0.0039 (7) | −0.0006 (5) |
C2 | 0.0267 (8) | 0.0248 (7) | 0.0257 (8) | 0.0037 (6) | 0.0090 (7) | 0.0001 (6) |
C3 | 0.0263 (8) | 0.0220 (7) | 0.0331 (9) | 0.0000 (6) | 0.0068 (7) | −0.0001 (6) |
C4 | 0.0337 (9) | 0.0235 (7) | 0.0274 (8) | 0.0011 (6) | 0.0063 (7) | −0.0045 (6) |
C5 | 0.0402 (10) | 0.0302 (8) | 0.0280 (9) | −0.0010 (7) | 0.0152 (8) | −0.0040 (7) |
C6 | 0.0320 (9) | 0.0252 (7) | 0.0315 (9) | −0.0032 (6) | 0.0126 (8) | −0.0006 (6) |
C7 | 0.0264 (8) | 0.0221 (7) | 0.0273 (8) | 0.0041 (6) | 0.0091 (7) | 0.0012 (6) |
C8 | 0.0221 (8) | 0.0208 (6) | 0.0254 (8) | 0.0008 (6) | 0.0054 (7) | 0.0002 (6) |
C9 | 0.0258 (8) | 0.0198 (6) | 0.0261 (8) | 0.0029 (6) | 0.0061 (7) | 0.0023 (6) |
C10 | 0.0388 (10) | 0.0286 (8) | 0.0276 (9) | −0.0045 (7) | 0.0120 (8) | −0.0053 (7) |
C11 | 0.0293 (8) | 0.0263 (7) | 0.0248 (8) | 0.0010 (7) | 0.0086 (7) | −0.0041 (6) |
F3—C3 | 1.3508 (19) | C5—C6 | 1.388 (2) |
F5—C5 | 1.230 (10) | C5—H5 | 0.9500 |
O1—C9 | 1.2361 (18) | C6—H6 | 0.9500 |
N1—C7 | 1.3234 (19) | C7—C8 | 1.386 (2) |
N1—C1 | 1.4240 (19) | C7—H7 | 0.9500 |
N1—H1 | 0.8800 | C8—C11 | 1.429 (2) |
N2—C11 | 1.151 (2) | C8—C9 | 1.455 (2) |
C1—C2 | 1.390 (2) | C9—C10 | 1.498 (2) |
C1—C6 | 1.391 (2) | C10—H10A | 0.9800 |
C2—C3 | 1.377 (2) | C10—H10B | 0.9800 |
C2—H2 | 0.9500 | C10—H10C | 0.9800 |
C3—C4 | 1.377 (2) | C10—H10D | 0.9800 |
C3—H3 | 0.9500 | C10—H10E | 0.9800 |
C4—C5 | 1.381 (2) | C10—H10F | 0.9800 |
C4—H4 | 0.9500 | ||
C7—N1—C1 | 125.15 (14) | C8—C7—H7 | 117.6 |
C7—N1—H1 | 117.4 | C7—C8—C11 | 116.65 (14) |
C1—N1—H1 | 117.4 | C7—C8—C9 | 123.64 (14) |
C2—C1—C6 | 120.75 (14) | C11—C8—C9 | 119.62 (13) |
C2—C1—N1 | 117.09 (14) | O1—C9—C8 | 120.47 (14) |
C6—C1—N1 | 122.16 (14) | O1—C9—C10 | 120.87 (14) |
C3—C2—C1 | 117.68 (15) | C8—C9—C10 | 118.66 (14) |
C3—C2—H2 | 121.2 | C9—C10—H10A | 109.5 |
C1—C2—H2 | 121.2 | C9—C10—H10B | 109.5 |
F3—C3—C2 | 118.33 (15) | H10A—C10—H10B | 109.5 |
F3—C3—C4 | 118.04 (14) | C9—C10—H10C | 109.5 |
C2—C3—C4 | 123.62 (15) | H10A—C10—H10C | 109.5 |
F3—C3—H3 | 0.2 | H10B—C10—H10C | 109.5 |
C2—C3—H3 | 118.2 | C9—C10—H10D | 109.5 |
C4—C3—H3 | 118.2 | H10A—C10—H10D | 141.1 |
C3—C4—C5 | 117.33 (15) | H10B—C10—H10D | 56.3 |
C3—C4—H4 | 121.3 | H10C—C10—H10D | 56.3 |
C5—C4—H4 | 121.3 | C9—C10—H10E | 109.5 |
F5—C5—C6 | 119.1 (5) | H10A—C10—H10E | 56.3 |
F5—C5—C4 | 119.3 (5) | H10B—C10—H10E | 141.1 |
C6—C5—C4 | 121.60 (16) | H10C—C10—H10E | 56.3 |
F5—C5—H5 | 1.2 | H10D—C10—H10E | 109.5 |
C6—C5—H5 | 119.2 | C9—C10—H10F | 109.5 |
C4—C5—H5 | 119.2 | H10A—C10—H10F | 56.3 |
C5—C6—C1 | 119.02 (15) | H10B—C10—H10F | 56.3 |
C5—C6—H6 | 120.5 | H10C—C10—H10F | 141.1 |
C1—C6—H6 | 120.5 | H10D—C10—H10F | 109.5 |
N1—C7—C8 | 124.79 (15) | H10E—C10—H10F | 109.5 |
N1—C7—H7 | 117.6 | N2—C11—C8 | 178.33 (16) |
C7—N1—C1—C2 | 179.33 (14) | C2—C1—C6—C5 | 0.0 (2) |
C7—N1—C1—C6 | −1.6 (2) | N1—C1—C6—C5 | −179.11 (14) |
C6—C1—C2—C3 | 0.1 (2) | C1—N1—C7—C8 | −178.58 (14) |
N1—C1—C2—C3 | 179.17 (13) | N1—C7—C8—C11 | 177.07 (14) |
C1—C2—C3—F3 | 179.93 (13) | N1—C7—C8—C9 | 0.6 (2) |
C1—C2—C3—C4 | 0.0 (2) | C7—C8—C9—O1 | −1.3 (2) |
F3—C3—C4—C5 | 180.00 (14) | C11—C8—C9—O1 | −177.64 (14) |
C2—C3—C4—C5 | −0.1 (2) | C7—C8—C9—C10 | 178.45 (14) |
C3—C4—C5—F5 | −178.5 (6) | C11—C8—C9—C10 | 2.1 (2) |
C3—C4—C5—C6 | 0.1 (2) | C7—C8—C11—N2 | −129 (6) |
F5—C5—C6—C1 | 178.6 (6) | C9—C8—C11—N2 | 48 (6) |
C4—C5—C6—C1 | 0.0 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1 | 0.88 | 2.05 | 2.7065 (17) | 131 |
C2—H2···O1i | 0.95 | 2.41 | 3.300 (2) | 156 |
C6—H6···N2ii | 0.95 | 2.67 | 3.618 (2) | 173 |
C7—H7···N2ii | 0.95 | 2.46 | 3.395 (2) | 167 |
C10—H10C···O1iii | 0.98 | 2.58 | 3.554 (2) | 172 |
Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) −x+1, −y+1, −z+1; (iii) x, y−1, z. |
C13H12FNO4 | Z = 2 |
Mr = 265.24 | F(000) = 276 |
Triclinic, P1 | Dx = 1.466 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 6.3000 (12) Å | Cell parameters from 769 reflections |
b = 9.4753 (18) Å | θ = 2.9–25.0° |
c = 10.765 (2) Å | µ = 0.12 mm−1 |
α = 88.947 (5)° | T = 153 K |
β = 79.810 (4)° | Needle, colourless |
γ = 71.931 (4)° | 0.38 × 0.11 × 0.06 mm |
V = 600.8 (2) Å3 |
Siemens CCD area-detector diffractometer | 2132 independent reflections |
Radiation source: fine-focus sealed tube | 1244 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.071 |
ω scans | θmax = 25.1°, θmin = 2.9° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | h = −7→7 |
Tmin = 0.956, Tmax = 0.993 | k = −11→11 |
6091 measured reflections | l = −12→12 |
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)] = 0.050 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.147 | H-atom parameters constrained |
S = 1.01 | w = 1/[σ2(Fo2) + (0.0122P)2 + 0.015P] where P = (Fo2 + 2Fc2)/3 |
2132 reflections | (Δ/σ)max < 0.001 |
174 parameters | Δρmax = 0.26 e Å−3 |
0 restraints | Δρmin = −0.25 e Å−3 |
C13H12FNO4 | γ = 71.931 (4)° |
Mr = 265.24 | V = 600.8 (2) Å3 |
Triclinic, P1 | Z = 2 |
a = 6.3000 (12) Å | Mo Kα radiation |
b = 9.4753 (18) Å | µ = 0.12 mm−1 |
c = 10.765 (2) Å | T = 153 K |
α = 88.947 (5)° | 0.38 × 0.11 × 0.06 mm |
β = 79.810 (4)° |
Siemens CCD area-detector diffractometer | 2132 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | 1244 reflections with I > 2σ(I) |
Tmin = 0.956, Tmax = 0.993 | Rint = 0.071 |
6091 measured reflections |
R[F2 > 2σ(F2)] = 0.050 | 0 restraints |
wR(F2) = 0.147 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.26 e Å−3 |
2132 reflections | Δρmin = −0.25 e Å−3 |
174 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. |
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 | ||
F1 | 0.0907 (3) | 1.33859 (19) | 1.06737 (15) | 0.0402 (5) | |
O1 | 1.1625 (3) | 0.9092 (2) | 0.89957 (17) | 0.0272 (5) | |
O2 | 1.4558 (3) | 0.7596 (2) | 0.76982 (17) | 0.0258 (5) | |
O3 | 1.4308 (3) | 0.6984 (2) | 0.56241 (17) | 0.0269 (5) | |
O4 | 1.1258 (3) | 0.8020 (2) | 0.47977 (18) | 0.0348 (6) | |
N1 | 0.7576 (3) | 1.0267 (2) | 0.8114 (2) | 0.0231 (6) | |
H1 | 0.8206 | 1.0250 | 0.8763 | 0.028* | |
C1 | 0.5266 (4) | 1.1156 (3) | 0.8223 (3) | 0.0229 (7) | |
C2 | 0.4194 (4) | 1.1860 (3) | 0.9389 (3) | 0.0247 (7) | |
H2 | 0.4977 | 1.1768 | 1.0058 | 0.030* | |
C3 | 0.1953 (4) | 1.2696 (3) | 0.9530 (3) | 0.0269 (7) | |
C4 | 0.0722 (4) | 1.2864 (3) | 0.8576 (3) | 0.0285 (7) | |
H4 | −0.0804 | 1.3425 | 0.8705 | 0.034* | |
C5 | 0.1819 (4) | 1.2174 (3) | 0.7421 (3) | 0.0275 (7) | |
H5 | 0.1020 | 1.2283 | 0.6758 | 0.033* | |
C6 | 0.4086 (4) | 1.1323 (3) | 0.7223 (3) | 0.0254 (7) | |
H6 | 0.4808 | 1.0870 | 0.6436 | 0.031* | |
C7 | 0.8829 (4) | 0.9468 (3) | 0.7106 (3) | 0.0253 (7) | |
H7 | 0.8133 | 0.9506 | 0.6408 | 0.030* | |
C8 | 1.1055 (4) | 0.8581 (3) | 0.6968 (3) | 0.0231 (7) | |
C9 | 1.2332 (4) | 0.8455 (3) | 0.7968 (3) | 0.0226 (7) | |
C10 | 1.5148 (4) | 0.6410 (3) | 0.6758 (3) | 0.0239 (7) | |
C11 | 1.2106 (4) | 0.7871 (3) | 0.5742 (3) | 0.0267 (7) | |
C12 | 1.4162 (5) | 0.5211 (3) | 0.7263 (3) | 0.0330 (8) | |
H12A | 1.4736 | 0.4838 | 0.8013 | 0.049* | |
H12B | 1.4584 | 0.4416 | 0.6637 | 0.049* | |
H12C | 1.2538 | 0.5614 | 0.7459 | 0.049* | |
C13 | 1.7680 (4) | 0.5894 (3) | 0.6401 (3) | 0.0312 (8) | |
H13A | 1.8177 | 0.6675 | 0.5994 | 0.047* | |
H13B | 1.8153 | 0.5039 | 0.5834 | 0.047* | |
H13C | 1.8334 | 0.5637 | 0.7147 | 0.047* |
U11 | U22 | U33 | U12 | U13 | U23 | |
F1 | 0.0341 (10) | 0.0465 (12) | 0.0320 (11) | −0.0040 (8) | 0.0002 (8) | −0.0101 (9) |
O1 | 0.0280 (10) | 0.0306 (12) | 0.0224 (12) | −0.0074 (9) | −0.0052 (9) | −0.0040 (10) |
O2 | 0.0206 (10) | 0.0267 (12) | 0.0275 (12) | −0.0021 (8) | −0.0064 (8) | −0.0090 (10) |
O3 | 0.0266 (10) | 0.0326 (12) | 0.0205 (11) | −0.0083 (9) | −0.0029 (8) | −0.0031 (10) |
O4 | 0.0354 (12) | 0.0453 (14) | 0.0246 (12) | −0.0112 (10) | −0.0099 (10) | −0.0020 (11) |
N1 | 0.0229 (12) | 0.0280 (14) | 0.0197 (13) | −0.0079 (10) | −0.0071 (10) | −0.0007 (11) |
C1 | 0.0219 (14) | 0.0223 (16) | 0.0282 (17) | −0.0119 (12) | −0.0058 (12) | 0.0047 (14) |
C2 | 0.0228 (15) | 0.0286 (18) | 0.0243 (16) | −0.0065 (13) | −0.0117 (12) | 0.0021 (14) |
C3 | 0.0285 (15) | 0.0264 (17) | 0.0256 (17) | −0.0093 (13) | −0.0025 (13) | −0.0026 (14) |
C4 | 0.0222 (15) | 0.0267 (17) | 0.0366 (19) | −0.0067 (13) | −0.0071 (14) | 0.0027 (15) |
C5 | 0.0254 (15) | 0.0285 (18) | 0.0343 (19) | −0.0122 (13) | −0.0140 (13) | 0.0049 (15) |
C6 | 0.0300 (16) | 0.0269 (17) | 0.0216 (16) | −0.0119 (13) | −0.0052 (13) | 0.0001 (14) |
C7 | 0.0298 (16) | 0.0277 (17) | 0.0244 (17) | −0.0155 (14) | −0.0087 (13) | −0.0003 (14) |
C8 | 0.0220 (15) | 0.0241 (16) | 0.0236 (16) | −0.0071 (13) | −0.0048 (12) | −0.0008 (14) |
C9 | 0.0218 (14) | 0.0204 (16) | 0.0262 (17) | −0.0069 (12) | −0.0050 (12) | −0.0015 (14) |
C10 | 0.0261 (15) | 0.0266 (17) | 0.0190 (15) | −0.0077 (13) | −0.0046 (12) | −0.0038 (14) |
C11 | 0.0259 (15) | 0.0302 (18) | 0.0280 (18) | −0.0130 (14) | −0.0079 (13) | 0.0022 (15) |
C12 | 0.0353 (17) | 0.0274 (18) | 0.0353 (19) | −0.0113 (14) | −0.0011 (14) | −0.0007 (15) |
C13 | 0.0268 (15) | 0.0333 (19) | 0.0304 (18) | −0.0056 (14) | −0.0030 (13) | −0.0050 (15) |
F1—C3 | 1.361 (3) | C4—H4 | 0.9300 |
O1—C9 | 1.213 (3) | C5—C6 | 1.386 (3) |
O2—C9 | 1.368 (3) | C5—H5 | 0.9300 |
O2—C10 | 1.441 (3) | C6—H6 | 0.9300 |
O3—C11 | 1.366 (3) | C7—C8 | 1.377 (3) |
O3—C10 | 1.446 (3) | C7—H7 | 0.9300 |
O4—C11 | 1.216 (3) | C8—C11 | 1.442 (4) |
N1—C7 | 1.315 (3) | C8—C9 | 1.435 (4) |
N1—C1 | 1.422 (3) | C10—C13 | 1.495 (3) |
N1—H1 | 0.8600 | C10—C12 | 1.506 (4) |
C1—C6 | 1.392 (4) | C12—H12A | 0.9600 |
C1—C2 | 1.390 (4) | C12—H12B | 0.9600 |
C2—C3 | 1.370 (3) | C12—H12C | 0.9600 |
C2—H2 | 0.9300 | C13—H13A | 0.9600 |
C3—C4 | 1.372 (4) | C13—H13B | 0.9600 |
C4—C5 | 1.377 (4) | C13—H13C | 0.9600 |
C9—O2—C10 | 117.1 (2) | C11—C8—C9 | 121.2 (2) |
C11—O3—C10 | 118.2 (2) | C7—C8—C9 | 121.6 (3) |
C7—N1—C1 | 125.6 (2) | O1—C9—O2 | 118.2 (2) |
C7—N1—H1 | 117.2 | O1—C9—C8 | 125.4 (2) |
C1—N1—H1 | 117.2 | O2—C9—C8 | 116.3 (2) |
C6—C1—C2 | 120.3 (2) | O2—C10—O3 | 109.8 (2) |
C6—C1—N1 | 122.7 (3) | O2—C10—C13 | 106.9 (2) |
C2—C1—N1 | 117.0 (2) | O3—C10—C13 | 105.9 (2) |
C3—C2—C1 | 118.3 (3) | O2—C10—C12 | 109.9 (2) |
C3—C2—H2 | 120.8 | O3—C10—C12 | 110.3 (2) |
C1—C2—H2 | 120.8 | C13—C10—C12 | 113.9 (2) |
F1—C3—C4 | 118.7 (2) | O4—C11—O3 | 116.9 (3) |
F1—C3—C2 | 118.2 (2) | O4—C11—C8 | 126.7 (3) |
C4—C3—C2 | 123.1 (3) | O3—C11—C8 | 116.3 (2) |
C3—C4—C5 | 117.8 (3) | C10—C12—H12A | 109.5 |
C3—C4—H4 | 121.1 | C10—C12—H12B | 109.5 |
C5—C4—H4 | 121.1 | H12A—C12—H12B | 109.5 |
C6—C5—C4 | 121.5 (3) | C10—C12—H12C | 109.5 |
C6—C5—H5 | 119.3 | H12A—C12—H12C | 109.5 |
C4—C5—H5 | 119.3 | H12B—C12—H12C | 109.5 |
C1—C6—C5 | 118.9 (3) | C10—C13—H13A | 109.5 |
C1—C6—H6 | 120.5 | C10—C13—H13B | 109.5 |
C5—C6—H6 | 120.5 | H13A—C13—H13B | 109.5 |
N1—C7—C8 | 127.4 (3) | C10—C13—H13C | 109.5 |
N1—C7—H7 | 116.3 | H13A—C13—H13C | 109.5 |
C8—C7—H7 | 116.3 | H13B—C13—H13C | 109.5 |
C11—C8—C7 | 117.0 (2) | ||
C7—N1—C1—C6 | −2.7 (4) | C11—C8—C9—O1 | 174.9 (3) |
C7—N1—C1—C2 | 176.8 (2) | C7—C8—C9—O1 | −0.3 (5) |
C6—C1—C2—C3 | 1.1 (4) | C11—C8—C9—O2 | −1.9 (4) |
N1—C1—C2—C3 | −178.5 (2) | C7—C8—C9—O2 | −177.0 (2) |
C1—C2—C3—F1 | −179.9 (2) | C9—O2—C10—O3 | 51.7 (3) |
C1—C2—C3—C4 | 0.2 (4) | C9—O2—C10—C13 | 166.2 (2) |
F1—C3—C4—C5 | 179.1 (2) | C9—O2—C10—C12 | −69.8 (3) |
C2—C3—C4—C5 | −1.1 (4) | C11—O3—C10—O2 | −48.3 (3) |
C3—C4—C5—C6 | 0.7 (4) | C11—O3—C10—C13 | −163.3 (2) |
C2—C1—C6—C5 | −1.4 (4) | C11—O3—C10—C12 | 73.0 (3) |
N1—C1—C6—C5 | 178.1 (2) | C10—O3—C11—O4 | −161.2 (2) |
C4—C5—C6—C1 | 0.5 (4) | C10—O3—C11—C8 | 21.1 (3) |
C1—N1—C7—C8 | −179.1 (3) | C7—C8—C11—O4 | 3.1 (4) |
N1—C7—C8—C11 | −176.8 (3) | C9—C8—C11—O4 | −172.2 (3) |
N1—C7—C8—C9 | −1.5 (5) | C7—C8—C11—O3 | −179.4 (2) |
C10—O2—C9—O1 | 155.3 (2) | C9—C8—C11—O3 | 5.3 (4) |
C10—O2—C9—C8 | −27.8 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1 | 0.86 | 2.15 | 2.775 (3) | 129 |
N1—H1···O1i | 0.86 | 2.53 | 3.334 (3) | 156 |
C2—H2···O1i | 0.93 | 2.44 | 3.296 (3) | 153 |
C2—H2···O2i | 0.93 | 2.59 | 3.449 (3) | 154 |
C5—H5···O4ii | 0.93 | 2.46 | 3.372 (3) | 165 |
C7—H7···O4 | 0.93 | 2.45 | 2.806 (3) | 103 |
Symmetry codes: (i) −x+2, −y+2, −z+2; (ii) −x+1, −y+2, −z+1. |
Experimental details
(I) | (II) | |
Crystal data | ||
Chemical formula | C11H9FN2O | C13H12FNO4 |
Mr | 204.20 | 265.24 |
Crystal system, space group | Monoclinic, P21/n | Triclinic, P1 |
Temperature (K) | 153 | 153 |
a, b, c (Å) | 13.907 (2), 5.0357 (8), 14.233 (2) | 6.3000 (12), 9.4753 (18), 10.765 (2) |
α, β, γ (°) | 90, 108.946 (4), 90 | 88.947 (5), 79.810 (4), 71.931 (4) |
V (Å3) | 942.8 (3) | 600.8 (2) |
Z | 4 | 2 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.11 | 0.12 |
Crystal size (mm) | 0.49 × 0.12 × 0.08 | 0.38 × 0.11 × 0.06 |
Data collection | ||
Diffractometer | Siemens CCD area-detector | Siemens CCD area-detector |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2003) | Multi-scan (SADABS; Sheldrick, 2003) |
Tmin, Tmax | 0.949, 0.991 | 0.956, 0.993 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 13411, 2554, 1650 | 6091, 2132, 1244 |
Rint | 0.072 | 0.071 |
(sin θ/λ)max (Å−1) | 0.688 | 0.596 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.047, 0.128, 1.01 | 0.050, 0.147, 1.01 |
No. of reflections | 2554 | 2132 |
No. of parameters | 148 | 174 |
No. of restraints | 2 | 0 |
H-atom treatment | H-atom parameters constrained | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.25, −0.20 | 0.26, −0.25 |
Computer programs: SMART (Bruker, 2003), SAINT (Bruker, 2003), SADABS (Sheldrick, 2003), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), DIAMOND (Brandenburg, 2009), PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
(I) | ||||
N1—H1···O1 | 0.88 | 2.05 | 2.765 (17) | 131 |
C7—H7···N2ii | 0.95 | 2.46 | 3.395 (2) | 167 |
C6—H6···N2ii | 0.95 | 2.67 | 3.618 (2) | 173 |
C2—H2···O1i | 0.95 | 2.41 | 3.300 (2) | 156 |
C10—H10C···O1iii | 0.98 | 2.58 | 3.554 (2) | 172 |
(II) | ||||
N1—H1···O1 | 0.86 | 2.15 | 2.776 (3) | 129 |
N1—H1···O1iv | 0.86 | 2.53 | 3.334 (3) | 156 |
C2—H2···O1iv | 0.93 | 2.44 | 3.296 (4) | 153 |
C2—H2···O2iv | 0.93 | 2.59 | 3.450 (4) | 154 |
C5—H5···O4v | 0.93 | 2.46 | 3.372 (4) | 165 |
Symmetry codes: (i) x, y+1/2, -z+1/2; (ii) -x+1, -y+1, -z+1; (iii) x, y-1, z; (iv) -x+2, -y+2, -z+2; (v) -x+1, -y+2, -z+1. |
Bond distance | WBO | |
F3—C3 | 1.3508 (19) | 0.893 |
O1—C9 | 1.2361 (18) | 1.654 |
N1—C7 | 1.3234 (19) | 1.307 |
N1—C1 | 1.4240 (19) | 1.041 |
N1—H1 | 1.028 | 0.694 |
N2—C11 | 1.151 (2) | 2.842 |
C7—C8 | 1.386 (2) | 1.460 |
C7—H7 | 1.085 | 0.904 |
C8—C11 | 1.429 (2) | 1.108 |
C8—C9 | 1.455 (2) | 1.107 |
C9—C10 | 1.498 (2) | 1.023 |
Bond distance | WBO | |
F1—C3 | 1.361 (3) | 0.888 |
O1—C9 | 1.213 (3) | 1.660 |
O4—C11 | 1.216 (3) | 1.696 |
N1—C7 | 1.315 (3) | 1.333 |
N1—C1 | 1.422 (3) | 1.033 |
N1—H1 | 1.028 | 0.707 |
C7—C8 | 1.377 (3) | 1.433 |
C8—C11 | 1.442 (4) | 1.078 |
C8—C9 | 1.435 (4) | 1.101 |
The heteroarylaminoethylene type of compounds substituted with fluorine are not only excellent precursors for the synthesis of biologically active 4-quinolones, but they are also biologically active themselves as they show e.g. photobleaching activity towards cells of Nicotiana tabacum, and fungicides [fungicidal?], germicides [germicidal?] or herbicides [herbicidal?] [properties?]. The title compounds were synthesized within the framework of our continuous study (Langer et al., 2006, 2009; Smrčok et al., 2007) of the structure and properties of potential precursors of fluoroquinolones, knowledge of which has proved essential in reaction pathway considerations and planning.
Perspective drawings of the title molecules are shown in Fig.1 for (I) and in Fig.2 for (II). The structure of (I) shows a disorder of the phenyl ring (rotation by 180°) with occupancy of 0.890 (1) for the main component and the methyl group at C10 has been refined with occupancy of 50% for two orientations with 60° relative to each other. Considering the calculated dipole moments for the molecules of (I) and (II) (4.5 and 2.3 D), it can be assumed that the main packing force in both structures is electrostatic. The basic building unit in both structures comprises molecules joined pairwise via different hydrogen bonds and the constituting [resulting?] pairs are cross-linked to form three-dimensional hydrogen-bonded networks. The fundamental structural motif in the structure of (I) is pairs of molecules arranged in an antiparallel fashion which enables C—H···N≡C interactions (Fig. 3). Every N atom is an acceptor of two hydrogen bonds of two slightly different lengths (Table 1). The pairs of molecules are cross-linked by two weak C—H···O hydrogen bonds aiming at the O1 oxygen atom, which is also involved in the very bent intramolecular N1—H1···O1 hydrogen bond (Table 1). This arrangement can be described as a ribbon of molecules running approximately parallel to [101]. The pair of molecules in the structure of (II) is formed by the intermolecular bifurcated C2—H2···O1iv/O2iv and the combined inter- and intramolecular N1—H1···O1/O1iv hydrogen bonds (Fig. 4). These basic pairs of molecules form sheets through the C5—H5···O4v hydrogen bond. Although the arrangement of neighboring sheets is dictated mainly by electrostatic forces they also connected though C12—H12B···Ovi hydrogen bonding.
In both structures F atoms appear in such positions that they could form weak C—F···H—C interactions (Howard et al., 1996; Dunitz & Taylor, 1997) with the H atoms of the two neighbouring methyl groups, i.e. two H10A atoms in the structure of (I), and the H12C and H13C atoms in the structure of (II). The H···F separations, 2.59/2.80 Å in (I) and 2.63/2.71 Å (II), are well within the limits found for this type of non-bonded contact (Shimoni & Glusker, 1994).
NBO (natural bond orbitals) analysis (Foster & Weinhold, 1980) carried out for the isolated molecules reveals a general delocalization pattern, which can be characterized (i) by the delocalization of the lone pair of the N atom into the C═C antibonding orbital resulting in the lowering of the bond order of this bond and in the increase of the bond order of the N1—C7 bond, and (ii) by shifting of the electrons from the C═O double bonds towards the pπ orbital of the O atoms resulting in the relatively large partial negative charge on O1 [NBO charges are -0.621 |e| in (I) and -0.622 |e| in (II)] and also in a decrease of its bond order (Tables 2 and 3). This shift is further enhanced by formation of an intramolecular O1···H1—N1 hydrogen bond. All these changes are qualitatively described by a superposition of resonance structures, depicted in Fig. 5. The most obvious geometric consequences of such electron delocalizations are shortening of the formally single N1—C7 bond and also lengthening of the formally double C7═C8 bond, reflected in the decrease of the bond order (Tables 2 and 3). Another consequence of electron redistribution is structural rigidity of the N1—C7—C8-(C9—O1)(C11—N2) moiety in (I), which is further enhanced by formation of an intramolecular N1—H1···O1 hydrogen bond.
The additional characteristic feature of the C1—N1—C7—C8 fragment is increased values of the skeletal angles, namely C1—N1—C7 [125.15 (14)° in (I), 125.6 (2)° in (II))] and N1—C7—C8 [124.79 (15)° in (I) and 127.4 (3)° in (II)] relative to the expected ideal value of 120°. The main reason is the increased s content in the hybrid orbitals on the N1 and C7 atoms as a consequence of the shortening of the N1—C7 bond. This increase in s character in turn brings about an increase in the p character in two other formally sp2 hybrids and thus lowers the angle between them (Bent, 1961; Langer et al., 2009).
The phenyl ring connected to the aminomethylene group is, in both structures, only slightly rotated from the plane of the N1—C7—C8—C9—C11 atoms, the torsion angle C7—N1—C1—C6 being -1.6 (2)° in (I) and -2.7 (4)° in (II). Full optimizations of the molecular geometry in vacuum, however, give remarkably larger torsion angles, ~13° (I) and ~11° (II), but a closer inspection of the torsion potential around the C1—N1 bond reveals that it is, in both cases, very flat. Its flatness can be documented by the fact that the strictly planar structure of (I) has a total energy of only 0.06 kJ mol-1 higher than the minimum and the calculated harmonic torsion frequency is only 14 cm-1. Such flatness of the torsion potentials is a compromise between the two competing interactions – on the one hand, the repulsion of the H1—H2 and the H6—H7 H atoms tending to rotate the ring from the planar position and, on the other hand, delocalization of a lone pair of the N atom into the phenyl ring, stabilizing the planar arrangement.
An interesting feature of this torsion potential is the low barrier for ~180° rotation of the substituted phenyl ring, leading to conformations (Ia) and (IIa). According to the molecular calculation in vacuum, these conformations are even slightly more stable than the molecules of (I) and (II), i.e. 0.6 and 0.4 kJ mol-1, respectively. In (I), this conformation (Ia) is present as a minor component with an occupancy of 0.110 (1). The rotation barriers separating these conformers are also rather small, 14.7 and 15.0 kJ mol-1, and are further reduced by a polar medium. For instance, our polarizable continuum model (PCM; Miertuš et al., 1981; Foresman et al., 1996) calculation revealed that in water the barrier further reduces to 10.2 and 11.7 kJ mol-1, respectively. The preference of the (I) and (II) over (Ia) and (IIa) in the real structures is thus apparently a result of the packing forces in the crystals.