Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270100005217/qb0204sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270100005217/qb0204Isup2.hkl |
CCDC reference: 145652
n-Butyllithium (2.5 M in hexane, 2.8 ml, 7 mmol) was added dropwise to a solution of diisopropylamine (1 ml, 7 mmol) in THF (10 ml) at 273 K under argon. After being stirred for 10 min, 2-methyl-1-pyrroline (3.5 mmol) in THF (7 ml) was added. The resulting mixture was stirred at 273 K for 30 min, and then cooled to 195 K. N-(p-Anisidino)-2-chloro-2,2-difluoroacetimidoyl chloride (3.5 mmol) in THF (7 ml) was added and stirred at 195 K. After 1 h, the reaction was quenched by addition of saturated ammonium chloride solution. The aqueous layer was extracted with dichloromethane (3 × 25 ml). The combined organic extracts were washed with brine, then dried (Na2SO4), and evaporated under reduced pressure to furnish the crude product. Flash chromatography [n-hexane-EtOAc (3:1)] on silica gel gave a yellow solid (79%): m.p. 361–363 K. Single crystals of (I) suitable for X-ray diffraction were grown by cooling a hexane solution.
The amino group hydrogen atom was found in a difference Fourier synthesis and refined with a restrained N—H bond length. Other H atoms were refined using a riding model (C—H 0.93–0.98 Å).
Data collection: CAD-4-96 Software (Enraf Nonius, 1996); cell refinement: CAD-4-96 Software; data reduction: MolEN (Fair, 1989); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); software used to prepare material for publication: SHELXL97.
C14H15ClF2N2O | Dx = 1.426 Mg m−3 |
Mr = 300.73 | Melting point: 88.9 K |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 7.6548 (15) Å | Cell parameters from 25 reflections |
b = 10.436 (2) Å | θ = 9.5–12.2° |
c = 17.543 (4) Å | µ = 0.29 mm−1 |
β = 91.34 (3)° | T = 293 K |
V = 1401.0 (5) Å3 | Prism, yellow |
Z = 4 | 0.78 × 0.46 × 0.42 mm |
F(000) = 624 |
Enraf-Nonius CAD-4 diffractometer | Rint = 0.020 |
Radiation source: fine-focus sealed tube | θmax = 25.0°, θmin = 2.3° |
Graphite monochromator | h = −9→9 |
ω scans | k = −12→5 |
3826 measured reflections | l = 0→20 |
2453 independent reflections | 3 standard reflections every 247 reflections |
1774 reflections with I > 2σ(I) | intensity decay: 1.6% |
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)] = 0.070 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.208 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | w = 1/[σ2(Fo2) + (0.1017P)2 + 1.8583P] where P = (Fo2 + 2Fc2)/3 |
2453 reflections | (Δ/σ)max < 0.001 |
185 parameters | Δρmax = 0.59 e Å−3 |
183 restraints | Δρmin = −0.65 e Å−3 |
C14H15ClF2N2O | V = 1401.0 (5) Å3 |
Mr = 300.73 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 7.6548 (15) Å | µ = 0.29 mm−1 |
b = 10.436 (2) Å | T = 293 K |
c = 17.543 (4) Å | 0.78 × 0.46 × 0.42 mm |
β = 91.34 (3)° |
Enraf-Nonius CAD-4 diffractometer | Rint = 0.020 |
3826 measured reflections | 3 standard reflections every 247 reflections |
2453 independent reflections | intensity decay: 1.6% |
1774 reflections with I > 2σ(I) |
R[F2 > 2σ(F2)] = 0.070 | 183 restraints |
wR(F2) = 0.208 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | Δρmax = 0.59 e Å−3 |
2453 reflections | Δρmin = −0.65 e Å−3 |
185 parameters |
Experimental. 1H NMR (250 MHz) 1.89 (m, 2H), 2.62 (t, J = 7.8, 2H), 3.58 (t, J = 7.0, 2H), 3.69 (s, 3H), 5.10 (s, 1H), 6.71–6.82 (m, 4H), 10.10 (br s, 1H); 13C NMR (62.8 MHz) 21.8 (t), 34.1 (t), 50.7 (t), 55.3 (q), 82.9 (t, 3JCF = 4.8), 113.4 (d), 121.6 (t, 1JCF = 302.1), 122.9 (d), 140.3 (s), 153.3 (t, 2JCF = 21.9), 155.67 (s), 166.5 (s); 19F NMR (235 MHz) −51.46; HRMS (FAB) calcd for (M+) C14H15ClF2N2O 300.0840, found 300.0851. Anal. Calcd for C14H15ClF2N2O: C, 55.91; H, 5.03; N, 9.31. Found: C, 56.11; H, 4.91; N, 9.19. |
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 | ||
N1 | 0.2623 (6) | −0.4364 (5) | −0.0242 (2) | 0.0526 (12) | |
H1 | 0.323 (8) | −0.431 (7) | 0.025 (2) | 0.08 (2)* | |
N2 | 0.2558 (6) | −0.3098 (5) | 0.1105 (2) | 0.0521 (11) | |
C1 | 0.1192 (6) | −0.3690 (5) | −0.0401 (3) | 0.0472 (12) | |
C2 | 0.0615 (7) | −0.3994 (6) | −0.1177 (3) | 0.0606 (15) | |
H2A | −0.0539 | −0.4378 | −0.1173 | 0.073* | |
H2B | 0.0549 | −0.3217 | −0.1479 | 0.073* | |
C3 | 0.1827 (8) | −0.4866 (6) | −0.1504 (3) | 0.0633 (16) | |
H3A | 0.2434 | −0.4464 | −0.1920 | 0.076* | |
H3B | 0.1229 | −0.5624 | −0.1696 | 0.076* | |
C4 | 0.3116 (9) | −0.5220 (6) | −0.0853 (3) | 0.0645 (16) | |
H4A | 0.2984 | −0.6110 | −0.0704 | 0.077* | |
H4B | 0.4314 | −0.5073 | −0.0998 | 0.077* | |
C5 | 0.0530 (7) | −0.2764 (5) | 0.0074 (3) | 0.0495 (13) | |
H5 | −0.0416 | −0.2284 | −0.0106 | 0.059* | |
C6 | 0.1191 (6) | −0.2494 (5) | 0.0818 (3) | 0.0457 (12) | |
C7 | 0.0252 (7) | −0.1463 (6) | 0.1257 (3) | 0.0522 (13) | |
C8 | 0.5290 (8) | −0.3399 (7) | 0.4582 (3) | 0.0665 (17) | |
H8A | 0.6025 | −0.3224 | 0.5021 | 0.080* | |
H8B | 0.5334 | −0.4298 | 0.4466 | 0.080* | |
H8C | 0.4110 | −0.3159 | 0.4687 | 0.080* | |
C11 | 0.3288 (6) | −0.2938 (5) | 0.1850 (3) | 0.0450 (12) | |
C12 | 0.4770 (7) | −0.2197 (6) | 0.1966 (3) | 0.0538 (13) | |
H12 | 0.5217 | −0.1732 | 0.1563 | 0.065* | |
C13 | 0.5591 (7) | −0.2142 (6) | 0.2674 (3) | 0.0546 (14) | |
H13 | 0.6578 | −0.1632 | 0.2742 | 0.065* | |
C14 | 0.4976 (6) | −0.2826 (5) | 0.3277 (3) | 0.0448 (12) | |
C15 | 0.3512 (7) | −0.3567 (5) | 0.3167 (3) | 0.0550 (14) | |
H15 | 0.3066 | −0.4032 | 0.3571 | 0.066* | |
C16 | 0.2697 (7) | −0.3622 (6) | 0.2454 (3) | 0.0539 (14) | |
H16 | 0.1718 | −0.4141 | 0.2386 | 0.065* | |
O | 0.5880 (5) | −0.2694 (4) | 0.3957 (2) | 0.0606 (11) | |
F1 | −0.1339 (4) | −0.1189 (4) | 0.0950 (2) | 0.0875 (14) | |
F2 | −0.0122 (5) | −0.1804 (4) | 0.19691 (19) | 0.0759 (11) | |
Cl | 0.1415 (2) | −0.00253 (16) | 0.13098 (11) | 0.0822 (7) |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.052 (2) | 0.066 (3) | 0.039 (2) | 0.006 (2) | −0.0051 (19) | −0.006 (2) |
N2 | 0.050 (2) | 0.067 (3) | 0.039 (2) | 0.008 (2) | −0.0070 (18) | −0.008 (2) |
C1 | 0.047 (3) | 0.059 (3) | 0.035 (2) | −0.006 (2) | −0.002 (2) | 0.002 (2) |
C2 | 0.069 (4) | 0.074 (4) | 0.039 (3) | −0.003 (3) | −0.009 (2) | −0.003 (3) |
C3 | 0.073 (4) | 0.073 (4) | 0.044 (3) | −0.014 (3) | 0.004 (3) | −0.013 (3) |
C4 | 0.077 (4) | 0.067 (4) | 0.050 (3) | 0.010 (3) | 0.001 (3) | −0.014 (3) |
C5 | 0.045 (3) | 0.063 (3) | 0.040 (3) | 0.006 (2) | −0.007 (2) | 0.001 (2) |
C6 | 0.043 (3) | 0.056 (3) | 0.038 (2) | −0.001 (2) | −0.001 (2) | −0.003 (2) |
C7 | 0.047 (3) | 0.063 (4) | 0.046 (3) | 0.004 (2) | −0.003 (2) | −0.003 (2) |
C8 | 0.068 (4) | 0.090 (5) | 0.041 (3) | 0.014 (3) | −0.006 (3) | 0.006 (3) |
C11 | 0.043 (3) | 0.054 (3) | 0.037 (2) | 0.007 (2) | −0.005 (2) | −0.006 (2) |
C12 | 0.051 (3) | 0.067 (4) | 0.044 (3) | −0.010 (3) | 0.001 (2) | 0.008 (3) |
C13 | 0.044 (3) | 0.072 (4) | 0.048 (3) | −0.015 (3) | −0.003 (2) | 0.003 (3) |
C14 | 0.045 (3) | 0.051 (3) | 0.038 (2) | 0.004 (2) | −0.007 (2) | 0.000 (2) |
C15 | 0.062 (3) | 0.058 (3) | 0.045 (3) | −0.015 (3) | −0.005 (2) | 0.011 (2) |
C16 | 0.053 (3) | 0.060 (3) | 0.048 (3) | −0.016 (3) | −0.010 (2) | 0.000 (2) |
O | 0.060 (2) | 0.075 (3) | 0.045 (2) | −0.005 (2) | −0.0188 (17) | 0.0047 (19) |
F1 | 0.054 (2) | 0.116 (3) | 0.092 (3) | 0.029 (2) | −0.0170 (18) | −0.039 (2) |
F2 | 0.100 (3) | 0.076 (2) | 0.0538 (19) | 0.003 (2) | 0.0341 (18) | −0.0038 (17) |
Cl | 0.0846 (12) | 0.0610 (11) | 0.1015 (15) | −0.0072 (8) | 0.0109 (10) | −0.0067 (9) |
N1—C1 | 1.326 (7) | C7—F1 | 1.350 (6) |
N1—C4 | 1.451 (7) | C7—Cl | 1.746 (6) |
N2—C6 | 1.312 (7) | C8—O | 1.404 (7) |
N2—C11 | 1.419 (6) | C11—C16 | 1.363 (7) |
C1—C5 | 1.380 (8) | C11—C12 | 1.384 (7) |
C1—C2 | 1.457 (7) | C12—C13 | 1.379 (7) |
C2—C3 | 1.429 (8) | C13—C14 | 1.370 (7) |
C3—C4 | 1.537 (8) | C14—C15 | 1.371 (7) |
C5—C6 | 1.417 (7) | C14—O | 1.372 (6) |
C6—C7 | 1.515 (7) | C15—C16 | 1.386 (7) |
C7—F2 | 1.337 (6) | ||
C1—N1—C4 | 113.6 (4) | F2—C7—Cl | 107.4 (4) |
C6—N2—C11 | 126.1 (4) | F1—C7—Cl | 107.1 (4) |
N1—C1—C5 | 123.9 (4) | C6—C7—Cl | 112.9 (4) |
N1—C1—C2 | 108.2 (5) | C16—C11—C12 | 117.6 (4) |
C5—C1—C2 | 127.6 (5) | C16—C11—N2 | 121.6 (5) |
C3—C2—C1 | 109.1 (5) | C12—C11—N2 | 120.3 (5) |
C2—C3—C4 | 105.5 (5) | C13—C12—C11 | 120.7 (5) |
N1—C4—C3 | 103.1 (5) | C14—C13—C12 | 121.1 (5) |
C1—C5—C6 | 124.6 (5) | C13—C14—C15 | 118.7 (5) |
N2—C6—C5 | 121.5 (5) | C13—C14—O | 116.3 (4) |
N2—C6—C7 | 122.0 (4) | C15—C14—O | 125.0 (5) |
C5—C6—C7 | 116.5 (4) | C14—C15—C16 | 120.0 (5) |
F2—C7—F1 | 102.6 (4) | C11—C16—C15 | 122.0 (5) |
F2—C7—C6 | 113.6 (5) | C14—O—C8 | 117.4 (4) |
F1—C7—C6 | 112.5 (4) | ||
C4—N1—C1—C5 | −176.2 (5) | N2—C6—C7—Cl | 74.0 (6) |
C4—N1—C1—C2 | −2.9 (5) | C5—C6—C7—Cl | −105.3 (5) |
N1—C1—C2—C3 | −2.4 (4) | C6—N2—C11—C16 | 87.1 (7) |
C5—C1—C2—C3 | 170.7 (5) | C6—N2—C11—C12 | −101.1 (7) |
C1—C2—C3—C4 | 6.2 (5) | C16—C11—C12—C13 | −1.1 (8) |
C1—N1—C4—C3 | 6.5 (6) | N2—C11—C12—C13 | −173.3 (5) |
C2—C3—C4—N1 | −7.4 (6) | C11—C12—C13—C14 | 0.7 (9) |
N1—C1—C5—C6 | −6.0 (8) | C12—C13—C14—C15 | −0.4 (9) |
C2—C1—C5—C6 | −178.0 (4) | C12—C13—C14—O | −179.4 (5) |
C11—N2—C6—C5 | −177.5 (5) | C13—C14—C15—C16 | 0.7 (9) |
C11—N2—C6—C7 | 3.3 (8) | O—C14—C15—C16 | 179.6 (5) |
C1—C5—C6—N2 | 2.3 (8) | C12—C11—C16—C15 | 1.4 (8) |
C1—C5—C6—C7 | −178.5 (5) | N2—C11—C16—C15 | 173.5 (5) |
N2—C6—C7—F2 | −48.7 (7) | C14—C15—C16—C11 | −1.2 (9) |
C5—C6—C7—F2 | 132.1 (5) | C13—C14—O—C8 | −179.1 (5) |
N2—C6—C7—F1 | −164.7 (5) | C15—C14—O—C8 | 1.9 (8) |
C5—C6—C7—F1 | 16.1 (7) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···N2 | 0.97 (4) | 2.04 (6) | 2.709 (6) | 124 (5) |
Experimental details
Crystal data | |
Chemical formula | C14H15ClF2N2O |
Mr | 300.73 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 293 |
a, b, c (Å) | 7.6548 (15), 10.436 (2), 17.543 (4) |
β (°) | 91.34 (3) |
V (Å3) | 1401.0 (5) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.29 |
Crystal size (mm) | 0.78 × 0.46 × 0.42 |
Data collection | |
Diffractometer | Enraf-Nonius CAD-4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3826, 2453, 1774 |
Rint | 0.020 |
(sin θ/λ)max (Å−1) | 0.594 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.070, 0.208, 1.04 |
No. of reflections | 2453 |
No. of parameters | 185 |
No. of restraints | 183 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.59, −0.65 |
Computer programs: CAD-4-96 Software (Enraf Nonius, 1996), CAD-4-96 Software, MolEN (Fair, 1989), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXL97.
N1—C1 | 1.326 (7) | C1—C2 | 1.457 (7) |
N1—C4 | 1.451 (7) | C2—C3 | 1.429 (8) |
N2—C6 | 1.312 (7) | C3—C4 | 1.537 (8) |
N2—C11 | 1.419 (6) | C5—C6 | 1.417 (7) |
C1—C5 | 1.380 (8) | ||
C1—N1—C4 | 113.6 (4) | C2—C3—C4 | 105.5 (5) |
C6—N2—C11 | 126.1 (4) | N1—C4—C3 | 103.1 (5) |
N1—C1—C5 | 123.9 (4) | C1—C5—C6 | 124.6 (5) |
N1—C1—C2 | 108.2 (5) | N2—C6—C5 | 121.5 (5) |
C5—C1—C2 | 127.6 (5) | N2—C6—C7 | 122.0 (4) |
C3—C2—C1 | 109.1 (5) | C5—C6—C7 | 116.5 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···N2 | 0.97 (4) | 2.04 (6) | 2.709 (6) | 124 (5) |
Fluorine-containing amino compounds have found a wide range of synthetic and biochemical applications due to the unique biological properties imparted by fluorine (Soloshonok et al., 1997, 1998; Bégué et al., 1996). Due to the increasing interest in the synthesis and reactivity of 1,3-difunctionalized fluorine-containing organic compounds (Uneyama et al., 1993; Fustero et al., 1996), we have focused our attention on the fluorinated vinylogous amidines.
We have recently developed the reaction of fluorinated imidoyl chlorides with ketimines to afford the first reported fluorinated vinylogous amidines (Fustero et al., 1999). Although, several tautomeric α–γ structures were possible, the β enaminic structure was determined by NMR analyses. However, the sterochemical assignment (Z or E) was not fully confirmed. Two-dimensional HOESY NMR 1H–19 F experiments suggest the Z configuration for the β enamino tautomer (Fustero et al. 1999). We have now determined the first crystal structure of a fluorinated vinylogous amidine which confirms the assigned geometry.
In the molecular structure of the title compound, (I), the pyrrolidine ring is planar (mean deviation 0.028 Å), with the N1—C1 bond length [1.326 (7) Å] shorter than N1—C4 [1.451 (7) Å]. This suggests an electronic elocalization along the imino–enamino group with bond lengths C1—C5, C5—C6 and C6—N2 of 1.380 (8), 1.417 (7) and 1.312 (7) Å, respectively. The pyrrolidine ring NH group acts as a hydrogen-bond donor to the iminic N atom in the same molecule. The resulting intramolecular hydrogen bond N1—H1···N2 [H1···N2 2.04 (6), N1···N2 2.709 (6) Å and N1—H1···N2 124 (5)°] makes a planar six-membered ring N2—C6—-C5–C1—N1—H1 (mean deviation 0.014 Å). The pyrrolidine ring and the hydrogen-bonded ring adopt a nearly coplanar conformation (dihedral angle 3.6°); this plane is almost perpendicular to the aromatic ring (83.5°).