2-(2,4-Di­chloro­phenoxy)-N-(4,6-di­methyl­pyridin-2-yl)­acet­amide

Lynch, D.E.; Bagga, S.; Parsons, S.

doi:10.1107/S1600536803016350

2-(2,4-Dichlorophenoxy)-N-(4,6-dimethylpyridin-2-yl)acetamide

The structure of the title compound, C₁₅H₁₄Cl₂N₂O₂, comprises an essentially flat molecule [dihedral angle of 3.64 (9)° between the two aromatic rings] with an intramolecular hydrogen-bonding interaction from the amine N-H group to the phenoxy O atom. Molecules are arranged in lamellar sheets parallel to the (110) plane.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536803016350/cf6274sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536803016350/cf6274Isup2.hkl Contains datablock I

CCDC reference: 222862

checkCIF report

Key indicators

Single-crystal X-ray study
T = 220 K
Mean (C-C) = 0.004 Å
R factor = 0.039
wR factor = 0.109
Data-to-parameter ratio = 13.1

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT027_ALERT_3_A _diffrn_reflns_theta_full too Low ............      24.95 Deg.
PLAT029_ALERT_3_A _diffrn_measured_fraction_theta_full Low .....       0.96

Alert level C
PLAT063_ALERT_3_C Crystal Probably too Large for Beam Size .....       0.70 mm
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .....          ?

   2 ALERT level A = In general: serious problem
   0 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
   3 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion

Comment top

A search of the April 2003 release of the Cambridge Structural Database (Allen, 2002) reveals that there are eight structures based on N-(4,6-dimethylpyridin-2-yl)carboxamide, all published by one research group. These structures are N-(4,6-dimethylpyridin-2-yl)-2-(3-nitrophenyl)acetamide (Rodier et al., 1986), N-(4,6-dimethylpyridin-2-yl)-2-(4-nitrophenyl)propionamide (Rodier, Robert & Le Bautet, 1990), (E)—N-(4,6-dimethylpyridin-2-yl)-3-phenylpropenamide hemihydrate (Rodier, Robert-Piessard & Le Baut, 1990), N-(4,6-dimethylpyridin-2-yl)-2-furamide (Rodier et al., 1991), N-(4,6-dimethylpyridin-2-yl)-2-thiophenecarboxamide (Rodier, Cense et al., 1992), N-(4,6-dimethylpyridin-2-yl)(1-methylindol-2-yl)carboxamide (Rodier, Robert & Le Baut, 1992), N-(4,6-dimethylpyridin-2-yl)-2-(3-nitrophenyl)acetamide (Rodier et al., 1993) and N-(4,6-dimethylpyridin-2-yl)-5-methylpyrazine-2-carboxamide (Rodier et al., 1994). In a series of studies on the syntheses of additional derivatives of N-(4,6-dimethylpyridin-2-yl)carboxamide and also N-(4,6-dimethylpyrimidin-2-yl)carboxamide as potential anti-inflammatory agents, we prepared the title compound, (I), and its structure is reported here.

The structure of (I) comprises an essentially flat molecule (Fig. 1) with an intramolecular hydrogen-bonding interaction from the amine N—H group to the phenoxy O atom (Table 1). Molecules of (I) are arranged in lamellar sheets parallel to the (110) plane. The dihedral angle between the substituted phenyl and pyridyl rings is 3.64 (9)°.

Experimental top

Four molar equivalents of oxalyl chloride (2.29 g, 18.1 mmol) were added dropwise to a stirred solution of (2,4-dichlorophenoxy)acetic acid (1.0 g, 4.5 mmol) and a catalytic amount of dry pyridine (dried over KOH) in 20 ml dry dichloromethane (dried over molecular sieves). After stirring for 30 min, the solvent was removed under reduced pressure, yielding a yellow solution of (2,4-dichlorophenoxy)acetic chloride. This solution was then added dropwise to a stirred solution of 2-amino-4,6-dimethylpyridine (0.55 g, 4.5 mmol) and triethylamine (0.46 g, 4.5 mmol) in 20 ml dry dichloromethane. After 30 min, the solution was filtered and the solvent removed under reduced pressure, yielding a white powder. The product was purified using column chromatography (SiO₂) and collected in the eluted ethyl acetate fraction after initial chloroform elutions. The solid product was further washed with 30 ml cold ethanol to afford 0.82 g of (I) (81%); m.p. 435–436 K; ¹H NMR (CDCl₃, 250 MHz): δ (p.p.m.) 2.33 (s, 3H, CH₃), 2.42 (s, 3H, CH₃), 4.62 (s, 2H, CH₂), 6.77 (s, 1H, Ar—H), 6.89 (d, J 8.8, 1H, Ar—H), 7.33 (d, J 8.8, 1H, Ar—H), 7.41 (d, J 2.5, 1H, py—H), 7.87 (s, 1H, py—H), 8.89 (bs, 1H, NH); m/z 325 (MH₊, 100%), 327 (MH₊, 75%). Crystals suitable for X-ray diffraction studies were grown from ethyl acetate.

Computing details top

Data collection: DIF4 (Stoe & Cie, 1990); cell refinement: DIF4; data reduction: REDU4 (Stoe & Cie, 1990); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON97 (Spek, 1997); software used to prepare material for publication: SHELXL97.

Figures top

Fig. 1. The molecular configuration and atom-numbering scheme for the title compound, showing 50% probability displacement ellipsoids.

2-(2,4-Dichlorophenoxy)-N-(4,6-dimethylpyridin-2-yl)acetamide top

Crystal data top

C₁₅H₁₄Cl₂N₂O₂	F(000) = 336
M_r = 325.18	D_x = 1.413 Mg m⁻³
Triclinic, P1	Melting point: 435 K
a = 7.445 (5) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.790 (6) Å	Cell parameters from 22 reflections
c = 12.549 (7) Å	θ = 15–16°
α = 89.28 (4)°	µ = 0.43 mm⁻¹
β = 87.08 (5)°	T = 220 K
γ = 68.74 (4)°	Prism, colourless
V = 764.4 (9) Å³	0.70 × 0.47 × 0.38 mm
Z = 2

Data collection top

Stoe Stadi-4 diffractometer	R_int = 0.019
Radiation source: fine-focus sealed tube	θ_max = 25.0°, θ_min = 2.9°
Graphite monochromator	h = −8→8
ω/θ scans	k = −10→10
3678 measured reflections	l = 0→14
2570 independent reflections	3 standard reflections every 60 min
2032 reflections with I > 2σ(I)	intensity decay: 3%

Refinement top

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)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.109	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.062P)² + 0.1634P] where P = (F_o² + 2F_c²)/3
2570 reflections	(Δ/σ)_max < 0.001
196 parameters	Δρ_max = 0.20 e Å⁻³
0 restraints	Δρ_min = −0.30 e Å⁻³

Crystal data top

C₁₅H₁₄Cl₂N₂O₂	γ = 68.74 (4)°
M_r = 325.18	V = 764.4 (9) Å³
Triclinic, P1	Z = 2
a = 7.445 (5) Å	Mo Kα radiation
b = 8.790 (6) Å	µ = 0.43 mm⁻¹
c = 12.549 (7) Å	T = 220 K
α = 89.28 (4)°	0.70 × 0.47 × 0.38 mm
β = 87.08 (5)°

Data collection top

Stoe Stadi-4 diffractometer	R_int = 0.019
3678 measured reflections	3 standard reflections every 60 min
2570 independent reflections	intensity decay: 3%
2032 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.039	0 restraints
wR(F²) = 0.109	H-atom parameters constrained
S = 1.05	Δρ_max = 0.20 e Å⁻³
2570 reflections	Δρ_min = −0.30 e Å⁻³
196 parameters

Special details top

Geometry. Mean plane data ex SHELXL97 for molecule (I) ############################################

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

7.0686 (0.0066) x + 5.4322 (0.0078) y − 0.8081 (0.0113) z = 7.1858 (0.0137)

* 0.0021 (0.0015) C1 * 0.0030 (0.0015) C2 * −0.0054 (0.0015) C3 * 0.0026 (0.0015) C4 * 0.0025 (0.0016) C5 * −0.0049 (0.0016) C6

Rms deviation of fitted atoms = 0.0036

6.9084 (0.0065) x + 5.8475 (0.0075) y − 0.9470 (0.0110) z = 7.1684 (0.0180)

Angle to previous plane (with approximate e.s.d.) = 3.64 (0.09)

* −0.0066 (0.0014) C12 * 0.0035 (0.0013) N13 * 0.0025 (0.0015) C14 * −0.0053 (0.0015) C15 * 0.0024 (0.0015) C16 * 0.0034 (0.0014) C17

Rms deviation of fitted atoms = 0.0042

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.7680 (3)	0.4768 (3)	0.02870 (16)	0.0350 (5)
C2	0.6560 (3)	0.6291 (3)	0.07107 (16)	0.0379 (5)
Cl2	0.64800 (11)	0.65788 (8)	0.20750 (5)	0.0635 (2)
C3	0.5510 (3)	0.7546 (3)	0.00706 (17)	0.0400 (5)
H3	0.4745	0.8566	0.0367	0.050*
C4	0.5601 (3)	0.7281 (3)	−0.10125 (17)	0.0383 (5)
Cl4	0.42869 (10)	0.88715 (8)	−0.18233 (5)	0.0579 (2)
C5	0.6701 (3)	0.5784 (3)	−0.14543 (17)	0.0446 (6)
H5	0.6749	0.5620	−0.2196	0.056*
C6	0.7729 (3)	0.4529 (3)	−0.08047 (17)	0.0427 (5)
H6	0.8469	0.3504	−0.1104	0.060 (8)*
O7	0.8631 (2)	0.36317 (18)	0.10017 (11)	0.0456 (4)
C8	0.9777 (3)	0.2030 (3)	0.06473 (17)	0.0384 (5)
H81	1.0773	0.2072	0.0120	0.047 (6)*
H82	0.8968	0.1527	0.0309	0.047 (7)*
C9	1.0706 (3)	0.1029 (3)	0.15923 (17)	0.0365 (5)
O10	1.1621 (3)	−0.04317 (19)	0.14712 (13)	0.0533 (5)
N11	1.0458 (3)	0.1869 (2)	0.25137 (13)	0.0365 (4)
H11	0.9797	0.2910	0.2473	0.046*
C12	1.1110 (3)	0.1314 (3)	0.35346 (16)	0.0338 (5)
N13	1.0269 (3)	0.2445 (2)	0.42800 (14)	0.0381 (4)
C14	1.0738 (3)	0.2054 (3)	0.52910 (17)	0.0410 (5)
C15	1.2042 (3)	0.0543 (3)	0.55577 (18)	0.0455 (6)
H15	1.2326	0.0305	0.6276	0.048 (7)*
C16	1.2938 (3)	−0.0629 (3)	0.47775 (18)	0.0418 (5)
C17	1.2448 (3)	−0.0218 (3)	0.37256 (17)	0.0385 (5)
H17	1.3011	−0.0963	0.3164	0.048*
C18	0.9729 (4)	0.3355 (3)	0.6116 (2)	0.0597 (7)
H181	1.0043	0.2913	0.6823	0.075*
H182	0.8345	0.3720	0.6046	0.075*
H183	1.0150	0.4271	0.6008	0.075*
C19	1.4333 (4)	−0.2283 (3)	0.5054 (2)	0.0548 (6)
H191	1.3631	−0.2927	0.5375	0.069*
H192	1.5226	−0.2169	0.5556	0.069*
H193	1.5044	−0.2826	0.4412	0.069*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0377 (12)	0.0342 (11)	0.0317 (11)	−0.0107 (10)	−0.0064 (9)	0.0035 (9)
C2	0.0423 (12)	0.0407 (12)	0.0286 (11)	−0.0120 (10)	−0.0058 (9)	−0.0008 (9)
Cl2	0.0839 (5)	0.0523 (4)	0.0327 (3)	0.0032 (3)	−0.0157 (3)	−0.0074 (3)
C3	0.0392 (12)	0.0355 (12)	0.0400 (12)	−0.0068 (10)	−0.0069 (10)	0.0019 (10)
C4	0.0365 (12)	0.0418 (12)	0.0376 (11)	−0.0147 (10)	−0.0106 (9)	0.0116 (10)
Cl4	0.0620 (4)	0.0567 (4)	0.0493 (4)	−0.0134 (3)	−0.0180 (3)	0.0224 (3)
C5	0.0527 (14)	0.0517 (14)	0.0292 (11)	−0.0184 (12)	−0.0046 (10)	0.0042 (10)
C6	0.0503 (14)	0.0395 (12)	0.0333 (11)	−0.0098 (11)	−0.0038 (10)	−0.0020 (10)
O7	0.0599 (10)	0.0331 (8)	0.0318 (8)	−0.0011 (8)	−0.0127 (7)	0.0004 (6)
C8	0.0412 (12)	0.0345 (11)	0.0337 (11)	−0.0066 (10)	−0.0028 (9)	−0.0038 (9)
C9	0.0348 (11)	0.0374 (12)	0.0345 (11)	−0.0093 (10)	−0.0047 (9)	−0.0023 (9)
O10	0.0609 (11)	0.0364 (9)	0.0464 (9)	0.0038 (8)	−0.0153 (8)	−0.0064 (7)
N11	0.0429 (10)	0.0301 (9)	0.0319 (9)	−0.0073 (8)	−0.0051 (8)	0.0014 (7)
C12	0.0355 (11)	0.0372 (11)	0.0311 (10)	−0.0159 (10)	−0.0044 (9)	0.0039 (9)
N13	0.0440 (11)	0.0389 (10)	0.0338 (10)	−0.0177 (9)	−0.0051 (8)	0.0010 (8)
C14	0.0462 (13)	0.0473 (13)	0.0349 (11)	−0.0228 (11)	−0.0073 (10)	0.0021 (10)
C15	0.0486 (14)	0.0593 (15)	0.0343 (12)	−0.0255 (13)	−0.0098 (10)	0.0073 (11)
C16	0.0349 (12)	0.0463 (13)	0.0467 (13)	−0.0172 (11)	−0.0084 (10)	0.0135 (11)
C17	0.0367 (12)	0.0399 (12)	0.0370 (12)	−0.0115 (10)	−0.0031 (9)	0.0029 (9)
C18	0.0782 (19)	0.0644 (17)	0.0391 (13)	−0.0281 (16)	−0.0070 (13)	−0.0090 (12)
C19	0.0472 (15)	0.0581 (16)	0.0546 (15)	−0.0128 (13)	−0.0153 (12)	0.0198 (12)

Geometric parameters (Å, º) top

C1—O7	1.354 (3)	N11—C12	1.411 (3)
C1—C6	1.385 (3)	N11—H11	0.87
C1—C2	1.391 (3)	C12—N13	1.330 (3)
C2—C3	1.374 (3)	C12—C17	1.381 (3)
C2—Cl2	1.729 (2)	N13—C14	1.340 (3)
C3—C4	1.376 (3)	C14—C15	1.380 (3)
C3—H3	0.94	C14—C18	1.507 (3)
C4—C5	1.379 (3)	C15—C16	1.387 (3)
C4—Cl4	1.738 (2)	C15—H15	0.94
C5—C6	1.377 (3)	C16—C17	1.396 (3)
C5—H5	0.94	C16—C19	1.497 (3)
C6—H6	0.94	C17—H17	0.94
O7—C8	1.419 (3)	C18—H181	0.97
C8—C9	1.508 (3)	C18—H182	0.97
C8—H81	0.98	C18—H183	0.97
C8—H82	0.98	C19—H191	0.97
C9—O10	1.223 (3)	C19—H192	0.97
C9—N11	1.348 (3)	C19—H193	0.97

O7—C1—C6	125.7 (2)	C12—N11—H11	115.2
O7—C1—C2	115.67 (19)	N13—C12—C17	124.8 (2)
C6—C1—C2	118.7 (2)	N13—C12—N11	111.47 (19)
C3—C2—C1	121.4 (2)	C17—C12—N11	123.75 (19)
C3—C2—Cl2	120.06 (17)	C12—N13—C14	117.3 (2)
C1—C2—Cl2	118.56 (18)	N13—C14—C15	121.9 (2)
C2—C3—C4	118.8 (2)	N13—C14—C18	115.8 (2)
C2—C3—H3	120.6	C15—C14—C18	122.3 (2)
C4—C3—H3	120.6	C14—C15—C16	120.7 (2)
C5—C4—C3	121.1 (2)	C14—C15—H15	119.6
C5—C4—Cl4	120.12 (18)	C16—C15—H15	119.6
C3—C4—Cl4	118.79 (18)	C15—C16—C17	117.3 (2)
C6—C5—C4	119.7 (2)	C15—C16—C19	121.5 (2)
C6—C5—H5	120.2	C17—C16—C19	121.3 (2)
C4—C5—H5	120.2	C12—C17—C16	118.0 (2)
C5—C6—C1	120.4 (2)	C12—C17—H17	121.0
C5—C6—H6	119.8	C16—C17—H17	121.0
C1—C6—H6	119.8	C14—C18—H181	109.5
C1—O7—C8	119.76 (17)	C14—C18—H182	109.5
O7—C8—C9	108.97 (17)	H181—C18—H182	109.5
O7—C8—H81	109.9	C14—C18—H183	109.5
C9—C8—H81	109.9	H181—C18—H183	109.5
O7—C8—H82	109.9	H182—C18—H183	109.5
C9—C8—H82	109.9	C16—C19—H191	109.5
H81—C8—H82	108.3	C16—C19—H192	109.5
O10—C9—N11	125.6 (2)	H191—C19—H192	109.5
O10—C9—C8	119.18 (19)	C16—C19—H193	109.5
N11—C9—C8	115.19 (18)	H191—C19—H193	109.5
C9—N11—C12	129.69 (18)	H192—C19—H193	109.5
C9—N11—H11	115.2

O7—C1—C2—C3	−179.43 (19)	O7—C8—C9—N11	−7.2 (3)
C6—C1—C2—C3	0.1 (3)	O10—C9—N11—C12	−1.7 (4)
O7—C1—C2—Cl2	−0.3 (3)	C8—C9—N11—C12	179.32 (19)
C6—C1—C2—Cl2	179.28 (17)	C9—N11—C12—N13	−168.0 (2)
C1—C2—C3—C4	−0.8 (3)	C9—N11—C12—C17	11.7 (3)
Cl2—C2—C3—C4	−179.97 (16)	C17—C12—N13—C14	−1.1 (3)
C2—C3—C4—C5	0.8 (3)	N11—C12—N13—C14	178.64 (17)
C2—C3—C4—Cl4	−179.59 (16)	C12—N13—C14—C15	0.2 (3)
C3—C4—C5—C6	0.0 (3)	C12—N13—C14—C18	−178.9 (2)
Cl4—C4—C5—C6	−179.65 (17)	N13—C14—C15—C16	0.7 (3)
C4—C5—C6—C1	−0.7 (4)	C18—C14—C15—C16	179.7 (2)
O7—C1—C6—C5	−179.9 (2)	C14—C15—C16—C17	−0.7 (3)
C2—C1—C6—C5	0.6 (3)	C14—C15—C16—C19	−179.0 (2)
C6—C1—O7—C8	−0.9 (3)	N13—C12—C17—C16	1.1 (3)
C2—C1—O7—C8	178.58 (19)	N11—C12—C17—C16	−178.60 (19)
C1—O7—C8—C9	178.64 (18)	C15—C16—C17—C12	−0.2 (3)
O7—C8—C9—O10	173.7 (2)	C19—C16—C17—C12	178.2 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N11—H11···O7	0.87	2.07	2.552 (3)	114

Experimental details

Crystal data
Chemical formula	C₁₅H₁₄Cl₂N₂O₂
M_r	325.18
Crystal system, space group	Triclinic, P1
Temperature (K)	220
a, b, c (Å)	7.445 (5), 8.790 (6), 12.549 (7)
α, β, γ (°)	89.28 (4), 87.08 (5), 68.74 (4)
V (Å³)	764.4 (9)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.43
Crystal size (mm)	0.70 × 0.47 × 0.38

Data collection
Diffractometer	Stoe Stadi-4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	3678, 2570, 2032
R_int	0.019
(sin θ/λ)_max (Å⁻¹)	0.594

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.109, 1.05
No. of reflections	2570
No. of parameters	196
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.30

Computer programs: DIF4 (Stoe & Cie, 1990), DIF4, REDU4 (Stoe & Cie, 1990), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON97 (Spek, 1997), SHELXL97.