4-Chloro-3-fluoro-2-methyl­aniline–pyrrolidine-2,5-dione (1/1)

Benjamin A Mayes; Patrick McGarry; Adel Moussa; David J Watkin

doi:10.1107/S1600536808018795

. 2008 Jun 28;64(Pt 7):o1355. doi: 10.1107/S1600536808018795

4-Chloro-3-fluoro-2-methylaniline–pyrrolidine-2,5-dione (1/1)

Benjamin A Mayes ^a,^*, Patrick McGarry ^a, Adel Moussa ^a, David J Watkin ^b

PMCID: PMC2961731 PMID: 21202974

Abstract

Chlorination of 3-fluoro-2-methylaniline with N-chlorosuccinimide gave one major regioisomer whose structure was determined by X-ray crystallography. The product was found to have cocrystallized with succinimide, giving the title compound, C₇H₇ClFN·C₄H₅NO₂. The crystal structure is stabilized by N—H⋯O hydrogen-bonding and π–π stacking interactions with a centroid–centroid distance of 3.4501 (8) Å.

Related literature

For related literature, see: Lazar et al. (2004 ▶); Marterer et al. (2003 ▶); Nickson & Roche-Dolson (1985 ▶); Shapiro et al. (2006 ▶); Tukada & Mazaki (1997 ▶); Zanka & Kubota (1999 ▶); Görbitz (1999 ▶).

Experimental

Crystal data

C₇H₇ClFN·C₄H₅NO₂
M _r = 258.68
Triclinic,
a = 7.3853 (2) Å
b = 7.4390 (2) Å
c = 11.5571 (4) Å
α = 73.1036 (13)°
β = 85.9336 (12)°
γ = 71.3703 (14)°
V = 575.53 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.34 mm⁻¹
T = 120 K
0.75 × 0.44 × 0.41 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ▶) T _min = 0.47, T _max = 0.87
16689 measured reflections
2904 independent reflections
2610 reflections with I > 2σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.032
wR(F ²) = 0.087
S = 0.88
2904 reflections
154 parameters
H-atom parameters constrained
Δρ_max = 0.38 e Å⁻³
Δρ_min = −0.37 e Å⁻³

Data collection: COLLECT (Nonius, 2001 ▶); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ▶); molecular graphics: CAMERON (Watkin et al., 1996 ▶); software used to prepare material for publication: CRYSTALS.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808018795/lh2642sup1.cif

e-64-o1355-sup1.cif^{(14.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808018795/lh2642Isup2.hkl

e-64-o1355-Isup2.hkl^{(182KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N12—H1⋯O16ⁱ	0.85	2.11	2.945 (2)	168
N8—H9⋯O16ⁱ	0.84	2.18	2.915 (2)	147
N8—H11⋯O17	0.88	2.17	3.030 (2)	166

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Symmetry code: (i) Inline graphic .

Acknowledgments

We thank Dr Sarah F. Jenkinson, University of Oxford, for her assistance in the preparation of the manuscript.

supplementary crystallographic information

Comment

Chlorination of anilines with N-chlorosuccinimide (NCS) can provide access to poly-substituted aromatic compounds, useful as high-value synthetic intermediates (Lazar et al., 2004; Marterer et al., 2003; Nickson & Roche-Dolson, 1985; Shapiro et al., 2006; Zanka & Kubota, 1999). In the present example, treatment of 3-fluoro-2-methylaniline with NCS in polar solvents (e.g. N,N-dimethylformamide) resulted in chlorination para to the NH₂as the primary regioisomer in 10-fold excess relative to the undesired ortho isomer.

The sample was supplied in the form of large crystalline aggregates (4 mm across) coated with perfluoropolyether oil as a preservative. A large (0.8x0.8x0.4 mm) section was cut from the mass. The material did not have a strong cleavage - the crystals just fractured erratically. Because of the risk that further cutting might totally destroy the sample, an initial X-ray data set was measured from this large sample. The results confirmed the expected structure, but also showed a co-crystallized molecule of succinimide (Tukada & Mazaki, 1997).

At the end of the initial data collection, the sample was further subdivided into an irregular block approximately 0.41x0.44x0.75 mm. Prescans showed that the further cutting of the crystal had introduced fractures, but the sample was still amenable to analysis. Because of the degraded quality of the crystal, a data set with a target redundancy of 3 (as opposed to the usual 1) was collected. This highly redundant dataset would enable corrections to be made for the poor crystal quality.

Structure solution was slightly complicated because of the unexpected succinimide, but after that refinement and the location of all hydrogen atoms was normal. The two components are shown in Fig. 1. Fig. 2 shows the plane-to-plane alternate stacking of the components, with minimum inter-planar spacing of 3.37Å - presumable π - π stacking. The columns of molecules are interconnected by N-H···O hydrogen bonds which form discreet centrosymmetric 4-component clusters (Fig. 3).

Experimental

3-Fluoro-2-methylaniline (550 mg, 4.40 mmol) was dissolved in N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA) or 1-methyl-2-pyrrolidinone (NMP) (5 ml) and cooled to 0–5°C under argon. N-Chlorosuccinimide (586 mg, 4.39 mmol) was added and the mixture was allowed to warm to room temperature over 15 h (Fig. 4). Dilution with ethyl acetate, washing with water, drying (sodium sulfate), filtration and evaporation of the solvents gave a crude oil.

Crystals were grown from isopropyl ether by seeding and storing at 4°C for two weeks. The solvent was decanted and the crystals coated with 2 drops of FOMBLIN perfluoropolyether oil.

Additional methods of characterization were recorded: m.p. 75.5–76.0°C; ¹H (400 MHz, d3-MeCN): δ = 2.04 (3H, d, J 2.0 Hz, CH₃), 2.62 (4H, s, CH₂CH₂), 4.32 (2H, br-s, NH₂), 6.46 (1H, dd, J 8.6 Hz, J 0.8 Hz), 7.00 (1H, a-t, J 8.6 Hz), 8.83 (1H, br-s, NH). ¹³C (100 MHz, d3-MeCN): δ = 9.12, 9.18 (CH₃), 30.26 (CH₂CH₂), 107.99, 108.19 (C-2), 111.16 (C-6), 111.34, 111.37 (C-4), 127.97, 127.98 (C-3), 147.76, 147.82 (C-5), 156.09, 158.47 (C-1), 179.33 (2 xC=O) (using crystallographic numbering).