Diethyl 2-{[2-(trifluoro­meth­yl)anil­ino]methyl­idene}propane­dioate

The title compound, C₁₅H₁₆F₃NO₄, is an N-substituted derivative of ortho-trifluoro­methyl­aniline featuring a twofold Michael system. The least-squares planes defined by the atoms of the phenyl ring and the atoms of the Michael system enclose an angle of 15.52 (5)°. Apart from classical intra­molecular N—H...O and N—H...F hydrogen bonds, inter­molecular C—H...O contacts are observed, the latter connecting the mol­ecules into chains along [110]. The shortest inter­centroid distance between two aromatic systems is 3.6875 (9) Å.

Key indicators

• Single-crystal X-ray study
• T = 200 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.044
• wR factor = 0.128
• Data-to-parameter ratio = 18.2

checkCIF/PLATON results

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Alert level C
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         C7

Author Response: scattering sites assigned correctly

PLAT250_ALERT_2_C Large U3/U1 Ratio for Average U(i,j) Tensor ....        2.1

Author Response: no obvious reason for alert

PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600          9
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600         14
PLAT913_ALERT_3_C Missing # of Very Strong Reflections in FCF ....          4

Alert level G
PLAT005_ALERT_5_G No _iucr_refine_instructions_details in CIF ....          ?
PLAT007_ALERT_5_G Note: Number of Unrefined D-H Atoms ............          1
PLAT154_ALERT_1_G The su's on the Cell Angles are Equal ..........    0.00100 Deg.

Author Response: values checked - are correct

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   5 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   3 ALERT level G = General information/check it is not something unexpected

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   2 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   2 ALERT type 5 Informative message, check


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Alert level A
PUBL024_ALERT_1_A The number of authors is greater than 5.
              Please specify the role of each of the co-authors
              for your paper.

Author Response: Garudachari, Isloor & Satyanarayan - synthesis, research and project settled around compound; Eric Hosten - mounting and selecting of crystals which was very time-consuming due to quality of sample; Thomas Gerber - initiator of this cooperation and supervisor of Xray facility; Richard Betz - structure solution and refinement as well as write up of this manuscript

   1 ALERT level A = Data missing that is essential or data in wrong format
   0 ALERT level G = General alerts. Data that may be required is missing

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S1. Comment

Esters of trifluoroaniline are very important intermediates to synthesize 8-fluoroquinoline derivatives, this moiety is of great importance to chemists as well as biologists as it is one of the key building elements for many naturally occurring compounds. Members of this family have a wide range of applications in pharmaceuticals as antimalarial (Kaur et al., 2010), anti-tuberculosis (Eswaran et al., 2010), antitumor (Chou et al., 2010), anticancer (Chen et al., 2004) and antiviral (Shingalapur et al., 2009) agents. In view of the biological importance, we have synthesized the title compound to study its crystal structure.

Resonance between the aromatic system and the N-bonded twofold Michael system (an α,β-unsaturated carbonyl compound moiety, see for instance, McMurry, 1992) renders the carbon–nitrogen backbone of the molecule nearly planar, with the least-sqaures planes defined by the carbon atoms of the phenyl ring on the one hand and the non-hydrogen atoms of the twofold Michael system on the other hand enclosing an angle of only 15.52 (5) ° (Fig. 1). In the crystal, classical intramolecular hydrogen bridges of the N–H···O and N–H···F type can be observed between the secondary amine group and two of the fluorine atoms of the trifluoromethyl group and one of the double-bonded oxygen atoms. In addition, an intramolecular C–H···F contact (d_C···F: 2.6805 (19) Å) involving one of the hydrogen atoms on the aromatic systems is obvious that explains the in-plane conformation of one of the trifluoromethyl group's fluorine atoms with the plane defined by the carbon atoms of the phenyl group. Intermolecular C–H···O contacts whose range falls by more than 0.1 Å below the sum of van-der-Waals radii of the atoms participating in them are present in the crystal structure. In terms of graph-set analysis (Etter et al., 1990; Bernstein et al., 1995), the descriptor for the latter type of contacts is C¹₁(10) on the unitary level. In total, the molecules are connected to infinite chains along [1 1 0]. Information about metrical parameters of these interactions can be found in Table 1. The shortest intercentroid distance between two aromatic systems was measured at 3.6875 (9) Å (Fig. 2).

Related literature

For the crystal structure of another ortho-trifluoromethyl aniline derivative featuring a Michael system as substituent, see: Schweinfurth et al. (2011). For general information on Michael systems, see: McMurry (1992). For general pharmaceutical background to derivatives of the title compound, see: Kaur et al. (2010); Eswaran et al. (2010); Chou et al. (2010); Chen et al. (2004); Shingalapur et al. (2009). For the preparation of the title compound, see: Eswaran et al. (2009) For the graph-set analysis of hydrogen bonds, see: Etter et al. (1990); Bernstein et al. (1995).

S2. Experimental

A suspension of 2-(trifluoromethyl) aniline (1.0 g, 0.0062 mol) and diethyl(ethoxymethylene) malonate (4.02 g, 0.0186 mol) was heated to 110 °C for 4 h. The reaction mixture was cooled. The solid product obtained was filtered, washed with pet ether and recrystallized using ethanol. Yield: 1.81 g, 88.29%, m. p. 357–358 K, (Eswaran et al., 2009).

S3. Refinement

Carbon-bound H atoms were placed in calculated positions (C—H 0.95 Å for aromatic and vinylic C atoms, C—H 0.99 Å for methylene groups) and were included in the refinement in the riding model approximation, with U(H) set to 1.2U_eq(C). The H atoms of the methyl groups were allowed to rotate with a fixed angle around the C–C bond to best fit the experimental electron density (HFIX 137 in the SHELX program suite (Sheldrick, 2008)), with U(H) set to 1.5U_eq(C). The nitrogen-bound H atom was placed in a calculated position (N—H 0.88 Å) and was included in the refinement in the riding model approximation, with U(H) set to 1.2U_eq(N)

Computing details

Data collection: APEX2 (Bruker, 2010); cell refinement: SAINT (Bruker, 2010); data reduction: SAINT (Bruker, 2010); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. The molecular structure of the title compound, with atom labels and anisotropic displacement ellipsoids (drawn at 50% probability level).
	Fig. 2. Intermolecular C–H···O contacts, viewed along [-1 0 0]. Symmetry operators: ^i x - 1, y - 1, z; ^ii x + 1, y + 1, z.

Diethyl 2-{[2-(trifluoromethyl)anilino]methylidene}propanedioate

Crystal data

C15H16F3NO4	Z = 2
Mr = 331.29	F(000) = 344
Triclinic, P1	Dx = 1.433 Mg m^−3
Hall symbol: -P 1	Melting point: 357(1) K
a = 7.8080 (2) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.1485 (3) Å	Cell parameters from 7916 reflections
c = 10.5265 (3) Å	θ = 2.8–28.3°
α = 95.193 (1)°	µ = 0.13 mm^−1
β = 109.183 (1)°	T = 200 K
γ = 99.405 (1)°	Platelet, colourless
V = 767.84 (4) Å^3	0.55 × 0.39 × 0.09 mm

Data collection

Bruker APEXII CCD diffractometer	3825 independent reflections
Radiation source: fine-focus sealed tube	3240 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.014
ϕ and ω scans	θmax = 28.4°, θmin = 2.1°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −10→10
Tmin = 0.946, Tmax = 1.000	k = −13→13
13616 measured reflections	l = −14→14

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)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.128	H-atom parameters constrained
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0646P)^2 + 0.2686P] where P = (Fo^2 + 2Fc^2)/3
3825 reflections	(Δ/σ)max < 0.001
210 parameters	Δρmax = 0.39 e Å^−3
0 restraints	Δρmin = −0.34 e Å^−3

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

	x	y	z	Uiso*/Ueq
F1	0.3636 (2)	−0.04352 (13)	0.35986 (11)	0.0857 (5)
F2	0.3880 (2)	0.16548 (13)	0.34858 (11)	0.0744 (4)
F3	0.60489 (16)	0.07240 (15)	0.33735 (11)	0.0755 (4)
O1	0.86819 (16)	0.61635 (10)	0.03165 (10)	0.0418 (3)
O2	0.68442 (13)	0.44254 (9)	−0.12584 (9)	0.0335 (2)
O3	0.71583 (16)	0.42107 (11)	0.32438 (10)	0.0431 (3)
O4	0.82996 (15)	0.61975 (10)	0.27787 (9)	0.0374 (2)
N1	0.49938 (14)	0.23376 (10)	0.11834 (10)	0.0264 (2)
H1	0.5378	0.2582	0.2071	0.032*
C1	0.36699 (16)	0.11270 (12)	0.06191 (12)	0.0251 (2)
C2	0.32968 (18)	0.02013 (13)	0.14539 (13)	0.0295 (3)
C3	0.20078 (19)	−0.10035 (13)	0.08848 (15)	0.0345 (3)
H3	0.1757	−0.1621	0.1459	0.041*
C4	0.10908 (19)	−0.13115 (13)	−0.05021 (15)	0.0360 (3)
H4	0.0239	−0.2147	−0.0890	0.043*
C5	0.1430 (2)	−0.03872 (15)	−0.13194 (15)	0.0376 (3)
H5	0.0788	−0.0587	−0.2275	0.045*
C6	0.26878 (19)	0.08245 (14)	−0.07735 (13)	0.0335 (3)
H6	0.2882	0.1454	−0.1353	0.040*
C7	0.4211 (2)	0.05075 (16)	0.29631 (15)	0.0439 (4)
C8	0.57087 (16)	0.31427 (12)	0.04683 (12)	0.0247 (2)
H8	0.5348	0.2837	−0.0480	0.030*
C9	0.69146 (16)	0.43685 (12)	0.09707 (12)	0.0246 (2)
C10	0.75905 (16)	0.51016 (12)	0.00254 (12)	0.0263 (2)
C11	0.7483 (2)	0.50110 (15)	−0.22660 (14)	0.0353 (3)
H11A	0.8853	0.5197	−0.1952	0.042*
H11B	0.7065	0.5872	−0.2421	0.042*
C12	0.6691 (3)	0.4020 (2)	−0.35413 (17)	0.0588 (5)
H12A	0.5338	0.3800	−0.3810	0.088*
H12B	0.7180	0.3196	−0.3391	0.088*
H12C	0.7030	0.4411	−0.4265	0.088*
C13	0.74669 (17)	0.48967 (13)	0.24184 (13)	0.0287 (3)
C14	0.8920 (2)	0.67197 (15)	0.42245 (14)	0.0432 (4)
H14A	1.0000	0.6351	0.4733	0.052*
H14B	0.7915	0.6459	0.4588	0.052*
C15	0.9441 (4)	0.82171 (18)	0.43692 (19)	0.0652 (6)
H15A	1.0332	0.8459	0.3913	0.098*
H15B	1.0003	0.8600	0.5337	0.098*
H15C	0.8332	0.8578	0.3953	0.098*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1	0.1160 (11)	0.0754 (8)	0.0410 (6)	−0.0340 (7)	0.0158 (6)	0.0275 (6)
F2	0.1112 (10)	0.0703 (8)	0.0401 (6)	0.0085 (7)	0.0324 (6)	−0.0040 (5)
F3	0.0501 (6)	0.1190 (11)	0.0426 (6)	0.0030 (6)	−0.0001 (5)	0.0263 (6)
O1	0.0542 (6)	0.0302 (5)	0.0357 (5)	−0.0117 (4)	0.0186 (5)	0.0039 (4)
O2	0.0392 (5)	0.0344 (5)	0.0256 (4)	−0.0053 (4)	0.0160 (4)	0.0038 (4)
O3	0.0599 (7)	0.0368 (5)	0.0243 (5)	−0.0072 (5)	0.0115 (4)	0.0062 (4)
O4	0.0508 (6)	0.0286 (5)	0.0254 (5)	−0.0056 (4)	0.0111 (4)	0.0000 (4)
N1	0.0288 (5)	0.0256 (5)	0.0226 (5)	−0.0010 (4)	0.0092 (4)	0.0048 (4)
C1	0.0255 (5)	0.0230 (5)	0.0274 (6)	0.0017 (4)	0.0115 (4)	0.0046 (4)
C2	0.0320 (6)	0.0278 (6)	0.0307 (6)	0.0035 (5)	0.0137 (5)	0.0088 (5)
C3	0.0378 (7)	0.0252 (6)	0.0434 (7)	0.0022 (5)	0.0186 (6)	0.0106 (5)
C4	0.0340 (6)	0.0251 (6)	0.0459 (8)	−0.0017 (5)	0.0156 (6)	−0.0011 (5)
C5	0.0372 (7)	0.0377 (7)	0.0313 (7)	−0.0039 (6)	0.0108 (5)	−0.0015 (5)
C6	0.0350 (6)	0.0341 (7)	0.0278 (6)	−0.0034 (5)	0.0112 (5)	0.0058 (5)
C7	0.0511 (8)	0.0435 (8)	0.0324 (7)	−0.0059 (6)	0.0140 (6)	0.0135 (6)
C8	0.0260 (5)	0.0246 (5)	0.0245 (5)	0.0034 (4)	0.0108 (4)	0.0051 (4)
C9	0.0265 (5)	0.0236 (5)	0.0239 (6)	0.0030 (4)	0.0098 (4)	0.0050 (4)
C10	0.0282 (5)	0.0247 (5)	0.0270 (6)	0.0036 (4)	0.0111 (5)	0.0061 (4)
C11	0.0411 (7)	0.0387 (7)	0.0315 (7)	0.0042 (6)	0.0197 (6)	0.0133 (5)
C12	0.0817 (13)	0.0610 (11)	0.0340 (8)	−0.0048 (9)	0.0308 (9)	0.0038 (7)
C13	0.0301 (6)	0.0277 (6)	0.0254 (6)	0.0014 (5)	0.0080 (5)	0.0046 (5)
C14	0.0556 (9)	0.0387 (8)	0.0251 (6)	−0.0028 (6)	0.0083 (6)	−0.0011 (5)
C15	0.1017 (16)	0.0404 (9)	0.0358 (8)	−0.0061 (9)	0.0137 (9)	−0.0067 (7)

Geometric parameters (Å, º)

F1—C7	1.3179 (16)	C5—C6	1.3832 (18)
F2—C7	1.342 (2)	C5—H5	0.9500
F3—C7	1.329 (2)	C6—H6	0.9500
O1—C10	1.2042 (15)	C8—C9	1.3728 (16)
O2—C10	1.3492 (15)	C8—H8	0.9500
O2—C11	1.4464 (14)	C9—C13	1.4630 (17)
O3—C13	1.2207 (16)	C9—C10	1.4741 (16)
O4—C13	1.3327 (15)	C11—C12	1.484 (2)
O4—C14	1.4551 (16)	C11—H11A	0.9900
N1—C8	1.3357 (14)	C11—H11B	0.9900
N1—C1	1.4071 (15)	C12—H12A	0.9800
N1—H1	0.8800	C12—H12B	0.9800
C1—C6	1.3908 (17)	C12—H12C	0.9800
C1—C2	1.4029 (16)	C14—C15	1.488 (2)
C2—C3	1.3913 (18)	C14—H14A	0.9900
C2—C7	1.4909 (19)	C14—H14B	0.9900
C3—C4	1.378 (2)	C15—H15A	0.9800
C3—H3	0.9500	C15—H15B	0.9800
C4—C5	1.380 (2)	C15—H15C	0.9800
C4—H4	0.9500
C10—O2—C11	116.56 (10)	C8—C9—C10	118.54 (11)
C13—O4—C14	115.84 (10)	C13—C9—C10	122.74 (10)
C8—N1—C1	124.71 (10)	O1—C10—O2	122.13 (11)
C8—N1—H1	117.6	O1—C10—C9	126.34 (12)
C1—N1—H1	117.6	O2—C10—C9	111.52 (10)
C6—C1—C2	118.40 (11)	O2—C11—C12	107.34 (12)
C6—C1—N1	120.99 (11)	O2—C11—H11A	110.2
C2—C1—N1	120.61 (11)	C12—C11—H11A	110.2
C3—C2—C1	120.22 (12)	O2—C11—H11B	110.2
C3—C2—C7	118.76 (12)	C12—C11—H11B	110.2
C1—C2—C7	120.98 (11)	H11A—C11—H11B	108.5
C4—C3—C2	120.77 (12)	C11—C12—H12A	109.5
C4—C3—H3	119.6	C11—C12—H12B	109.5
C2—C3—H3	119.6	H12A—C12—H12B	109.5
C3—C4—C5	118.95 (12)	C11—C12—H12C	109.5
C3—C4—H4	120.5	H12A—C12—H12C	109.5
C5—C4—H4	120.5	H12B—C12—H12C	109.5
C4—C5—C6	121.24 (13)	O3—C13—O4	121.74 (12)
C4—C5—H5	119.4	O3—C13—C9	122.85 (11)
C6—C5—H5	119.4	O4—C13—C9	115.40 (10)
C5—C6—C1	120.37 (12)	O4—C14—C15	107.04 (12)
C5—C6—H6	119.8	O4—C14—H14A	110.3
C1—C6—H6	119.8	C15—C14—H14A	110.3
F1—C7—F3	108.38 (14)	O4—C14—H14B	110.3
F1—C7—F2	105.40 (15)	C15—C14—H14B	110.3
F3—C7—F2	103.63 (14)	H14A—C14—H14B	108.6
F1—C7—C2	113.24 (13)	C14—C15—H15A	109.5
F3—C7—C2	113.39 (13)	C14—C15—H15B	109.5
F2—C7—C2	112.06 (13)	H15A—C15—H15B	109.5
N1—C8—C9	126.33 (11)	C14—C15—H15C	109.5
N1—C8—H8	116.8	H15A—C15—H15C	109.5
C9—C8—H8	116.8	H15B—C15—H15C	109.5
C8—C9—C13	118.72 (10)
C8—N1—C1—C6	−14.70 (19)	C1—C2—C7—F2	57.59 (18)
C8—N1—C1—C2	165.95 (11)	C1—N1—C8—C9	175.78 (12)
C6—C1—C2—C3	1.70 (19)	N1—C8—C9—C13	−1.73 (19)
N1—C1—C2—C3	−178.93 (11)	N1—C8—C9—C10	178.62 (11)
C6—C1—C2—C7	−175.94 (13)	C11—O2—C10—O1	2.65 (19)
N1—C1—C2—C7	3.43 (19)	C11—O2—C10—C9	−176.71 (10)
C1—C2—C3—C4	0.5 (2)	C8—C9—C10—O1	−177.98 (13)
C7—C2—C3—C4	178.20 (13)	C13—C9—C10—O1	2.4 (2)
C2—C3—C4—C5	−1.9 (2)	C8—C9—C10—O2	1.34 (16)
C3—C4—C5—C6	1.0 (2)	C13—C9—C10—O2	−178.29 (11)
C4—C5—C6—C1	1.2 (2)	C10—O2—C11—C12	172.35 (13)
C2—C1—C6—C5	−2.6 (2)	C14—O4—C13—O3	3.8 (2)
N1—C1—C6—C5	178.08 (12)	C14—O4—C13—C9	−177.67 (12)
C3—C2—C7—F1	−1.0 (2)	C8—C9—C13—O3	12.48 (19)
C1—C2—C7—F1	176.66 (14)	C10—C9—C13—O3	−167.89 (13)
C3—C2—C7—F3	123.02 (15)	C8—C9—C13—O4	−166.01 (11)
C1—C2—C7—F3	−59.31 (19)	C10—C9—C13—O4	13.62 (18)
C3—C2—C7—F2	−120.09 (15)	C13—O4—C14—C15	−168.58 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···F2	0.88	2.35	2.9330 (15)	124
N1—H1···F3	0.88	2.45	2.9242 (15)	114
N1—H1···O3	0.88	1.99	2.6399 (14)	130
C3—H3···F1	0.95	2.33	2.6805 (19)	101
C4—H4···O1^i	0.95	2.60	3.2766 (17)	129

Symmetry code: (i) x−1, y−1, z.