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

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.

Key indicators

• Single-crystal X-ray study
• T = 120 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.033
• wR factor = 0.088
• Data-to-parameter ratio = 18.9

checkCIF/PLATON results

No syntax errors found



Alert level B
ABSTM02_ALERT_3_B  The ratio of expected to reported Tmax/Tmin(RR') is < 0.75
            Tmin and Tmax reported:      0.470     0.870
            Tmin(prime) and Tmax expected:      0.774     0.871
            RR(prime) =      0.608
            Please check that your absorption correction is appropriate.
PLAT061_ALERT_4_B Tmax/Tmin Range Test RR' too Large .............       0.61

Alert level C
PLAT063_ALERT_4_C Crystal Probably too Large for Beam Size .......       0.75 mm
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?

   0 ALERT level A = In general: serious problem
   2 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

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

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S1. 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 NH₂ as 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).

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).

S2. 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).

S3. Refinement

The relatively large ratio of minimum to maximum corrections applied in the multiscan process (1:1.85) reflect the poor quality of the sample.

Difficulties in selecting an integration box suitable for all frames were taken into account (Görbitz, 1999) by the multi-scan inter-frame scaling (DENZO/SCALEPACK, Otwinowski & Minor, 1997).

The H atoms were all located in a difference map, but those attached to carbon atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–0.98, N—H in the range 0.86–0.89 N—H to 0.86 Å) and U_iso(H) (in the range 1.2–1.5 times U_eq of the parent atom), after which the positions were refined with riding constraints.

Computing details

Data collection: COLLECT (Nonius, 2001); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK (Otwinowski & Minor, 1997); 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 (Betteridge et al., 2003).

Figures

	Fig. 1. The title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.
	Fig. 2. Plane-to-plane stacking of alternate molecules parallel to the a axis.
	Fig. 3. The hydrogen bonds (dotted lines) in the π -π stacks.
	Fig. 4. Synthetic scheme.

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

Crystal data

C7H7ClFN·C4H5NO2	Z = 2
Mr = 258.68	F(000) = 268
Triclinic, P1	Dx = 1.493 Mg m^−3
a = 7.3853 (2) Å	Mo Kα radiation, λ = 0.71073 Å
b = 7.4390 (2) Å	Cell parameters from 2870 reflections
c = 11.5571 (4) Å	θ = 5–29°
α = 73.1036 (13)°	µ = 0.34 mm^−1
β = 85.9336 (12)°	T = 120 K
γ = 71.3703 (14)°	Plate, colourless
V = 575.53 (3) Å^3	0.75 × 0.44 × 0.41 mm

Data collection

Nonius KappaCCD diffractometer	2610 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.033
ω scans	θmax = 28.7°, θmin = 5.4°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997)	h = −9→9
Tmin = 0.47, Tmax = 0.87	k = −10→9
16689 measured reflections	l = −15→15
2904 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.032	H-atom parameters constrained
wR(F^2) = 0.087	Method = Modified Sheldrick w = 1/[σ^2(F^2) + (0.05P)^2 + 0.35P], where P = [max(Fo^2,0) + 2Fc^2]/3
S = 0.88	(Δ/σ)max = 0.001
2904 reflections	Δρmax = 0.38 e Å^−3
154 parameters	Δρmin = −0.37 e Å^−3
0 restraints

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

	x	y	z	Uiso*/Ueq
C11	0.94307 (16)	0.30918 (17)	0.66142 (11)	0.0207
N12	0.99166 (15)	0.16670 (15)	0.59934 (9)	0.0223
C13	1.10284 (16)	−0.01507 (17)	0.66627 (11)	0.0205
C14	1.14595 (16)	−0.00013 (17)	0.78815 (10)	0.0204
C15	1.04097 (16)	0.21516 (17)	0.78494 (11)	0.0211
O16	1.15499 (13)	−0.16202 (13)	0.62979 (8)	0.0275
O17	0.83954 (13)	0.47656 (13)	0.62086 (8)	0.0280
H141	1.2797	−0.0325	0.7987	0.0245*
H142	1.0987	−0.0916	0.8511	0.0240*
H151	1.1221	0.2859	0.7939	0.0258*
H152	0.9471	0.2271	0.8474	0.0263*
H1	0.9510	0.1824	0.5287	0.0265*
C1	0.34402 (16)	0.96277 (18)	0.14329 (10)	0.0201
C2	0.28607 (16)	1.11710 (17)	0.19551 (11)	0.0207
C3	0.34232 (16)	1.08204 (17)	0.31427 (11)	0.0217
C4	0.45586 (16)	0.89539 (17)	0.37673 (10)	0.0210
C5	0.51642 (16)	0.74038 (17)	0.32214 (10)	0.0188
C6	0.45694 (16)	0.77380 (17)	0.20237 (10)	0.0194
C7	0.51289 (19)	0.60873 (19)	0.14308 (12)	0.0269
N8	0.63360 (16)	0.55949 (16)	0.38422 (10)	0.0277
Cl9	0.14163 (4)	1.34735 (4)	0.11329 (3)	0.0293
F10	0.28435 (11)	0.99849 (12)	0.02806 (6)	0.0291
H31	0.3012	1.1851	0.3475	0.0277*
H41	0.4953	0.8705	0.4581	0.0257*
H71	0.6503	0.5518	0.1414	0.0420*
H72	0.4641	0.5027	0.1863	0.0416*
H73	0.4639	0.6536	0.0618	0.0429*
H9	0.6698	0.4664	0.3519	0.0324*
H11	0.6736	0.5392	0.4585	0.0317*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C11	0.0199 (5)	0.0202 (5)	0.0235 (6)	−0.0059 (4)	0.0007 (4)	−0.0088 (4)
N12	0.0264 (5)	0.0201 (5)	0.0187 (5)	−0.0024 (4)	−0.0048 (4)	−0.0072 (4)
C13	0.0196 (5)	0.0201 (5)	0.0209 (5)	−0.0039 (4)	−0.0013 (4)	−0.0064 (4)
C14	0.0196 (5)	0.0216 (5)	0.0195 (5)	−0.0049 (4)	−0.0029 (4)	−0.0061 (4)
C15	0.0198 (5)	0.0232 (5)	0.0221 (6)	−0.0066 (4)	−0.0014 (4)	−0.0090 (4)
O16	0.0325 (5)	0.0212 (4)	0.0259 (5)	0.0005 (4)	−0.0056 (4)	−0.0108 (4)
O17	0.0302 (5)	0.0206 (4)	0.0305 (5)	−0.0012 (3)	−0.0058 (4)	−0.0090 (4)
C1	0.0196 (5)	0.0262 (6)	0.0156 (5)	−0.0089 (4)	−0.0015 (4)	−0.0051 (4)
C2	0.0180 (5)	0.0187 (5)	0.0228 (6)	−0.0049 (4)	−0.0023 (4)	−0.0023 (4)
C3	0.0217 (5)	0.0206 (5)	0.0237 (6)	−0.0051 (4)	0.0005 (4)	−0.0094 (4)
C4	0.0213 (5)	0.0228 (5)	0.0184 (5)	−0.0043 (4)	−0.0026 (4)	−0.0074 (4)
C5	0.0165 (5)	0.0190 (5)	0.0196 (5)	−0.0041 (4)	0.0003 (4)	−0.0050 (4)
C6	0.0181 (5)	0.0218 (5)	0.0205 (5)	−0.0081 (4)	0.0020 (4)	−0.0077 (4)
C7	0.0290 (6)	0.0277 (6)	0.0276 (6)	−0.0077 (5)	0.0010 (5)	−0.0144 (5)
N8	0.0317 (6)	0.0207 (5)	0.0241 (5)	0.0027 (4)	−0.0051 (4)	−0.0071 (4)
Cl9	0.02920 (17)	0.02088 (16)	0.03136 (17)	−0.00375 (11)	−0.00674 (12)	−0.00040 (11)
F10	0.0341 (4)	0.0346 (4)	0.0175 (3)	−0.0092 (3)	−0.0072 (3)	−0.0055 (3)

Geometric parameters (Å, º)

C11—N12	1.3890 (14)	C2—C3	1.3885 (17)
C11—C15	1.5141 (16)	C2—Cl9	1.7335 (12)
C11—O17	1.2075 (14)	C3—C4	1.3826 (16)
N12—C13	1.3689 (15)	C3—H31	0.913
N12—H1	0.852	C4—C5	1.4075 (16)
C13—C14	1.5082 (16)	C4—H41	0.952
C13—O16	1.2235 (14)	C5—C6	1.4096 (16)
C14—C15	1.5309 (16)	C5—N8	1.3629 (14)
C14—H141	0.947	C6—C7	1.5076 (16)
C14—H142	0.970	C7—H71	0.968
C15—H151	0.943	C7—H72	0.963
C15—H152	0.968	C7—H73	0.955
C1—C2	1.3848 (17)	N8—H9	0.842
C1—C6	1.3826 (16)	N8—H11	0.882
C1—F10	1.3569 (13)
N12—C11—C15	107.80 (9)	C1—C2—C3	118.84 (11)
N12—C11—O17	124.27 (11)	C1—C2—Cl9	119.74 (9)
C15—C11—O17	127.93 (11)	C3—C2—Cl9	121.41 (9)
C11—N12—C13	113.60 (10)	C2—C3—C4	119.37 (11)
C11—N12—H1	125.7	C2—C3—H31	117.6
C13—N12—H1	120.5	C4—C3—H31	123.1
N12—C13—C14	108.74 (9)	C3—C4—C5	121.32 (11)
N12—C13—O16	123.80 (11)	C3—C4—H41	119.8
C14—C13—O16	127.46 (11)	C5—C4—H41	118.9
C13—C14—C15	104.82 (9)	C4—C5—C6	119.65 (11)
C13—C14—H141	109.5	C4—C5—N8	120.21 (11)
C15—C14—H141	111.9	C6—C5—N8	120.13 (10)
C13—C14—H142	109.2	C5—C6—C1	117.02 (10)
C15—C14—H142	111.7	C5—C6—C7	120.92 (11)
H141—C14—H142	109.5	C1—C6—C7	122.05 (11)
C14—C15—C11	104.97 (9)	C6—C7—H71	111.7
C14—C15—H151	114.0	C6—C7—H72	111.2
C11—C15—H151	109.0	H71—C7—H72	106.7
C14—C15—H152	112.8	C6—C7—H73	111.5
C11—C15—H152	109.9	H71—C7—H73	108.1
H151—C15—H152	106.2	H72—C7—H73	107.4
C2—C1—C6	123.78 (11)	C5—N8—H9	120.4
C2—C1—F10	118.07 (10)	C5—N8—H11	120.3
C6—C1—F10	118.14 (10)	H9—N8—H11	119.3

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N12—H1···O16^i	0.85	2.11	2.945 (2)	168
N8—H9···O16^i	0.84	2.18	2.915 (2)	147
N8—H11···O17	0.88	2.17	3.030 (2)	166

Symmetry code: (i) −x+2, −y, −z+1.