2,2-Dimethyl-N-(4-methyl­pyridin-2-yl)propanamide

In the title compound, C₁₁H₁₆N₂O, the dihedral angle between the mean plane of the 4-methypyridine group and the plane of the amide link is 16.7 (1)°, and there is a short intra­molecular C-H...O contact. Hydrogen bonding (N-H...O) between amide groups forms chains parallel to the b axis. Pairs of methyl­pyridine groups from mol­ecules in adjacent chains are parallel but there is minimal [pi]-[pi] inter­action.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.046
• wR factor = 0.154
• Data-to-parameter ratio = 17.1

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S1. Structural commentary

Synthetic and naturally occurring pyridine derivatives have a broad range of biological activities (Thorat et al., 2013) including anti­cancer and anti­microbial (Abdel-Megeed et al., 2012) and anti­coagulant (de Candia et al., 2013) properties. Hence, pyridine derivatives are important compounds (Joule and Mills, 2000) and some synthetic approaches involve li­thia­tion of 2-acyl­amino­pyridines (Smith et al., 1995; Turner, 1983). The structures of a number of 2-acyl­amino­pyridines have been determined (Mazik & Sicking, 2004; Mazik et al., 2004; Hodorowicz et al., 2007; Koch et al., 2008; Liang et al., 2008; Seidler et al., 2011). During research focused on new synthetic routes towards novel substituted pyridine derivatives (Smith et al., 1994; Smith et al., 1995; Smith et al., 1999; El-Hiti, 2003; Smith et al., 2012; Smith et al., 2013) we have synthesized the title compound in high yield. In the 4-methyl-2-pivaloyl­amino­pyridine molecule (Figure 1), the least squares plane through the 4-methypyridine group makes a dihedral angle of 16.7 (1)° with the plane through the amide link and a short intra­molecular C5—H5···O1 contact is observed (Table 1). In the crystal structure (Figure 2) N—H···O hydrogen bonding between amide groups forms chains parallel to the b axis. Pairs of methyl-pyridine groups in molecules from adjacent chains are parallel but there is minimal π-π inter­action. The ring nitro­gen is not involved in strong hydrogen bonding.

S2. Synthesis and crystallization

To a cooled solution (0 °C) of 2-amino-4-methyl­pyridine (5.41 g, 50.0 mmol) and tri­ethyl­amine (10 ml) in di­chloro­methane (DCM, 80 ml) pivaloyl chloride (6.63 g, 55.0 mmol) was slowly added in a drop-wise manner over 10 min. The reaction mixture was stirred at 0 °C for an extra 1 h. The mixture was poured into H₂O (100 ml) and the organic layer was separated, washed with H₂O (2 × 50 ml), dried (MgSO₄) and evaporated under reduced pressure to remove the solvent. The solid obtained was purified by crystallization from Et₂O–hexane (2:1) to give 4-methyl-2-pivaloyl­amino­pyridine (9.04 g, 47.0 mmol; 94%) as colourless crystals, m.p. 103–104 °C [lit. 96–98 °C (hexane); Turner (1983)]. ¹H NMR (500 MHz, CDCl₃, δ, p.p.m.) 8.11–8.10 (br, 2 H, H-3 and H-6), 8.05 (br, exch., 1 H, NH), 6.85 (m, 1 H, H-5), 2.34 (s, 3 H, CH₃), 1.31 [s, 9 H, C(CH₃)₃]. ¹³CNMR (125 MHz, CDCl₃, δ, p.p.m.) 177.2 (s, C=O), 151.5 (s, C-4), 149.9 (s, C-2), 147.2 (d, C-6), 120.9 (d, C-5), 114.5 (d, C-3), 39.8 [s, C(CH₃)₃], 27.5 [q, C(CH₃)₃]), 21.4 (q, CH₃). EI⁺–MS (m/z, %): 192 (M⁺, 43), 177 (5), 149 (11), 135 (25), 108 (100), 92 (15), 81 (15), 57 (25). HRMS (EI⁺): Calculated for C₁₁H₁₆N₂O [M] 192.1263; found, 192.1260.

S3. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms were positioned geometrically and refined using a riding model with U_iso(H) = 1.2 times U_eq for the atom they are bonded to except for the methyl groups where 1.5 times U_eq was used with free rotation about the C—C bond.

Related literature

For biological applications of related compounds, see: de Candia et al. (2013); Thorat et al. (2013); Abdel-Megeed et al. (2012). For convenient routes for modifying pyridine derivatives, see: Smith et al. (2013); Smith et al. (2012); El-Hiti (2003); Joule & Mills (2000); Smith et al. (1994, 1995, 1999); Turner (1983). For the X-ray structures of related compounds, see: Mazik & Sicking (2004); Mazik et al. (2004); Hodorowicz et al. (2007); Koch et al. (2008); Liang et al. (2008); Seidler et al. (2011).

Computing details

Data collection: CrysAlis PRO (Agilent, 2014); cell refinement: CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012) and CHEMDRAW Ultra (CambridgeSoft, 2001).

Figures

	Fig. 1. A molecule showing atom labels and 50% probability displacement ellipsoids for non-H atoms.
	Fig. 2. Crystal structure packing showing NH..O hydrogen bonds as green dotted lines with the rest of the hydrogen atoms omitted for clarity.

2,2-Dimethyl-N-(4-methylpyridin-2-yl)propanamide

Crystal data

C11H16N2O	Dx = 1.115 Mg m^−3
Mr = 192.26	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, Pbca	Cell parameters from 1808 reflections
a = 10.7954 (3) Å	θ = 4.2–74.0°
b = 10.1809 (2) Å	µ = 0.58 mm^−1
c = 20.8390 (5) Å	T = 296 K
V = 2290.35 (10) Å^3	Block, colourless
Z = 8	0.27 × 0.19 × 0.14 mm
F(000) = 832

Data collection

Agilent SuperNova (Dual, Cu at zero, Atlas) diffractometer	1808 reflections with I > 2σ(I)
Radiation source: sealed X-ray tube	Rint = 0.017
ω scans	θmax = 74.0°, θmin = 4.2°
Absorption correction: gaussian (CrysAlis PRO; Agilent, 2014)	h = −7→13
Tmin = 0.930, Tmax = 0.957	k = −12→8
5219 measured reflections	l = −25→20
2253 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.046	w = 1/[σ^2(Fo^2) + (0.0734P)^2 + 0.4299P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.154	(Δ/σ)max < 0.001
S = 1.08	Δρmax = 0.16 e Å^−3
2253 reflections	Δρmin = −0.14 e Å^−3
132 parameters	Extinction correction: SHELXL2013 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0037 (5)

Special details

Experimental. Absorption correction: CrysAlisPro (Agilent, 2014): Numerical absorption correction based on Gaussian integration over a multifaceted crystal model. Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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.

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

	x	y	z	Uiso*/Ueq
C1	0.90730 (14)	0.81479 (14)	0.59591 (7)	0.0489 (4)
C2	1.0228 (2)	0.6963 (2)	0.52600 (11)	0.0816 (6)
H2	1.0345	0.6201	0.5021	0.098*
C3	1.1102 (2)	0.7922 (2)	0.52141 (11)	0.0792 (6)
H3	1.1786	0.7811	0.4948	0.095*
C4	1.09637 (16)	0.90571 (19)	0.55651 (9)	0.0632 (5)
C5	0.99149 (14)	0.91744 (16)	0.59451 (8)	0.0552 (4)
H5	0.9779	0.9929	0.6186	0.066*
C6	1.1912 (2)	1.0138 (3)	0.55444 (12)	0.0922 (7)
H6A	1.2409	1.0107	0.5926	0.138*
H6B	1.1499	1.0972	0.5520	0.138*
H6C	1.2431	1.0025	0.5175	0.138*
C7	0.74226 (15)	0.91931 (14)	0.66136 (8)	0.0515 (4)
C8	0.62472 (16)	0.88824 (16)	0.69967 (9)	0.0606 (5)
C9	0.6598 (2)	0.8017 (2)	0.75696 (11)	0.0851 (7)
H9A	0.7235	0.8442	0.7815	0.128*
H9B	0.6895	0.7185	0.7418	0.128*
H9C	0.5882	0.7883	0.7835	0.128*
C10	0.5677 (2)	1.0158 (2)	0.72312 (13)	0.0997 (9)
H10A	0.6251	1.0600	0.7509	0.149*
H10B	0.4929	0.9970	0.7463	0.149*
H10C	0.5490	1.0709	0.6870	0.149*
C11	0.53133 (19)	0.8146 (3)	0.65810 (13)	0.0933 (8)
H11A	0.4578	0.7976	0.6826	0.140*
H11B	0.5668	0.7329	0.6442	0.140*
H11C	0.5107	0.8670	0.6213	0.140*
N1	0.92138 (14)	0.70437 (14)	0.56251 (8)	0.0654 (4)
N2	0.79937 (12)	0.81473 (12)	0.63366 (7)	0.0554 (4)
H2A	0.7654	0.7394	0.6400	0.067*
O1	0.78283 (12)	1.03049 (11)	0.65664 (7)	0.0699 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0475 (8)	0.0469 (8)	0.0523 (8)	0.0056 (6)	0.0003 (6)	0.0012 (6)
C2	0.0788 (13)	0.0735 (12)	0.0924 (14)	0.0131 (10)	0.0224 (11)	−0.0152 (11)
C3	0.0626 (11)	0.0889 (14)	0.0861 (13)	0.0180 (10)	0.0226 (10)	0.0029 (11)
C4	0.0481 (9)	0.0720 (11)	0.0694 (10)	0.0027 (8)	0.0020 (7)	0.0171 (9)
C5	0.0518 (9)	0.0531 (9)	0.0607 (9)	0.0001 (7)	0.0028 (7)	0.0032 (7)
C6	0.0587 (11)	0.1052 (17)	0.1126 (18)	−0.0166 (11)	0.0083 (11)	0.0244 (15)
C7	0.0533 (8)	0.0390 (7)	0.0622 (8)	0.0022 (6)	0.0061 (7)	−0.0009 (6)
C8	0.0592 (10)	0.0478 (8)	0.0749 (10)	0.0016 (7)	0.0190 (8)	−0.0021 (7)
C9	0.0969 (16)	0.0788 (13)	0.0798 (13)	0.0035 (12)	0.0275 (12)	0.0104 (10)
C10	0.1026 (17)	0.0605 (12)	0.136 (2)	0.0135 (11)	0.0640 (16)	−0.0025 (12)
C11	0.0548 (11)	0.1121 (19)	0.1129 (18)	−0.0056 (11)	0.0126 (12)	−0.0159 (15)
N1	0.0646 (9)	0.0546 (8)	0.0770 (9)	0.0056 (7)	0.0107 (7)	−0.0124 (7)
N2	0.0551 (8)	0.0401 (7)	0.0711 (8)	−0.0038 (5)	0.0153 (6)	−0.0040 (6)
O1	0.0673 (8)	0.0389 (6)	0.1034 (10)	−0.0010 (5)	0.0213 (7)	−0.0030 (6)

Geometric parameters (Å, º)

C1—N1	1.3310 (19)	C7—N2	1.3590 (19)
C1—C5	1.385 (2)	C7—C8	1.532 (2)
C1—N2	1.406 (2)	C8—C10	1.518 (2)
C2—N1	1.336 (3)	C8—C11	1.526 (3)
C2—C3	1.361 (3)	C8—C9	1.531 (3)
C2—H2	0.9300	C9—H9A	0.9600
C3—C4	1.376 (3)	C9—H9B	0.9600
C3—H3	0.9300	C9—H9C	0.9600
C4—C5	1.387 (2)	C10—H10A	0.9600
C4—C6	1.503 (3)	C10—H10B	0.9600
C5—H5	0.9300	C10—H10C	0.9600
C6—H6A	0.9600	C11—H11A	0.9600
C6—H6B	0.9600	C11—H11B	0.9600
C6—H6C	0.9600	C11—H11C	0.9600
C7—O1	1.2177 (18)	N2—H2A	0.8600
N1—C1—C5	123.45 (15)	C11—C8—C9	108.85 (18)
N1—C1—N2	112.76 (13)	C10—C8—C7	109.09 (14)
C5—C1—N2	123.78 (14)	C11—C8—C7	110.66 (15)
N1—C2—C3	124.35 (19)	C9—C8—C7	108.69 (15)
N1—C2—H2	117.8	C8—C9—H9A	109.5
C3—C2—H2	117.8	C8—C9—H9B	109.5
C2—C3—C4	119.33 (18)	H9A—C9—H9B	109.5
C2—C3—H3	120.3	C8—C9—H9C	109.5
C4—C3—H3	120.3	H9A—C9—H9C	109.5
C3—C4—C5	117.68 (17)	H9B—C9—H9C	109.5
C3—C4—C6	121.72 (19)	C8—C10—H10A	109.5
C5—C4—C6	120.60 (19)	C8—C10—H10B	109.5
C1—C5—C4	118.87 (16)	H10A—C10—H10B	109.5
C1—C5—H5	120.6	C8—C10—H10C	109.5
C4—C5—H5	120.6	H10A—C10—H10C	109.5
C4—C6—H6A	109.5	H10B—C10—H10C	109.5
C4—C6—H6B	109.5	C8—C11—H11A	109.5
H6A—C6—H6B	109.5	C8—C11—H11B	109.5
C4—C6—H6C	109.5	H11A—C11—H11B	109.5
H6A—C6—H6C	109.5	C8—C11—H11C	109.5
H6B—C6—H6C	109.5	H11A—C11—H11C	109.5
O1—C7—N2	122.06 (15)	H11B—C11—H11C	109.5
O1—C7—C8	122.14 (14)	C1—N1—C2	116.32 (16)
N2—C7—C8	115.80 (13)	C7—N2—C1	127.83 (13)
C10—C8—C11	109.58 (19)	C7—N2—H2A	116.1
C10—C8—C9	109.95 (18)	C1—N2—H2A	116.1

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O1^i	0.86	2.22	3.0644 (17)	168
C5—H5···O1	0.93	2.28	2.842 (2)	118

Symmetry code: (i) −x+3/2, y−1/2, z.