1-Chloro-1,1-di­fluoro-N-(4-methoxy­phenyl)-3-(pyrrolidin-2-yl­idene)­propan-2-imine

In the title compound, C₁₄H₁₅ClF₂N₂O, the Z configuration has been confirmed. The molecular structure shows an intramolecular N-H...N hydrogen bond [H...N 2.04 (6), N...N 2.709 (6) Å and N-H...N 124 (5)°]. This interaction could be responsible for the Z configuration.

S1. Comment

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°).

S2. Experimental

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.

S3. Refinement

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).

Computing details

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.

N2-(4-Methoxyphenyl)-3-(2-pyrrolidinyliden)-1-chloro-1,1- -difluoro-2-propan imine

Crystal data

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) Å^3	Prism, yellow
Z = 4	0.78 × 0.46 × 0.42 mm
F(000) = 624

Data collection

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

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.070	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.208	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ^2(Fo^2) + (0.1017P)^2 + 1.8583P] where P = (Fo^2 + 2Fc^2)/3
2453 reflections	(Δ/σ)max < 0.001
185 parameters	Δρmax = 0.59 e Å^−3
183 restraints	Δρmin = −0.65 e Å^−3

Special details

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, ³J_CF = 4.8), 113.4 (d), 121.6 (t, ¹J_CF = 302.1), 122.9 (d), 140.3 (s), 153.3 (t, ²J_CF = 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	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)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

Geometric parameters (Å, º)

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)

Hydrogen-bond geometry (Å, º)

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)