organic compounds
2,2-Dimethyl-N-(4-methylpyridin-2-yl)propanamide
aDepartment of Optometry, College of Applied Medical Sciences, King Saud University, PO Box 10219, Riyadh 11433, Saudi Arabia, bSchool of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, Wales, and cDepartment of Chemistry, College of Science for Women, University of Babylon, Babylon, Iraq
*Correspondence e-mail: gelhiti@ksu.edu.sa, kariukib@cardiff.ac.uk
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 π–π interaction.
CCDC reference: 987696
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).
Experimental
Crystal data
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Data collection: CrysAlis PRO (Agilent, 2014); cell CrysAlis PRO; data reduction: CrysAlis PRO; 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).
Supporting information
CCDC reference: 987696
10.1107/S1600536814003729/mw2120sup1.cif
contains datablocks I, New_Global_Publ_Block. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536814003729/mw2120Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536814003729/mw2120Isup3.cml
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 π-π interaction. The ring nitrogen is not involved in strong hydrogen bonding.
(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 minimalTo 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.
Crystal data, data collection and structure
details are summarized in Table 1. H atoms were positioned geometrically and refined using a riding model with Uiso(H) = 1.2 times Ueq for the atom they are bonded to except for the methyl groups where 1.5 times Ueq was used with about the C—C bond.Data collection: CrysAlis PRO (Agilent, 2014); cell
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).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) Å3 | Block, colourless |
Z = 8 | 0.27 × 0.19 × 0.14 mm |
F(000) = 832 |
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 on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.046 | w = 1/[σ2(Fo2) + (0.0734P)2 + 0.4299P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 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+0.001xFc2λ3/sin(2θ)]-1/4 |
0 restraints | Extinction coefficient: 0.0037 (5) |
C11H16N2O | V = 2290.35 (10) Å3 |
Mr = 192.26 | Z = 8 |
Orthorhombic, Pbca | Cu Kα radiation |
a = 10.7954 (3) Å | µ = 0.58 mm−1 |
b = 10.1809 (2) Å | T = 296 K |
c = 20.8390 (5) Å | 0.27 × 0.19 × 0.14 mm |
Agilent SuperNova (Dual, Cu at zero, Atlas) diffractometer | 2253 independent reflections |
Absorption correction: gaussian (CrysAlis PRO; Agilent, 2014) | 1808 reflections with I > 2σ(I) |
Tmin = 0.930, Tmax = 0.957 | Rint = 0.017 |
5219 measured reflections |
R[F2 > 2σ(F2)] = 0.046 | 0 restraints |
wR(F2) = 0.154 | H-atom parameters constrained |
S = 1.08 | Δρmax = 0.16 e Å−3 |
2253 reflections | Δρmin = −0.14 e Å−3 |
132 parameters |
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. |
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) |
U11 | U22 | U33 | U12 | U13 | U23 | |
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) |
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 |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2A···O1i | 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. |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2A···O1i | 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. |
Acknowledgements
The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for its funding of this research through the research group project RGP-VPP-239.
References
Abdel-Megeed, M. F., Badr, B. E., Azaam, M. M. & El-Hiti, G. A. (2012). Bioorg. Med. Chem. 20, 2252–2258. Web of Science CAS PubMed Google Scholar
Agilent (2014). CrysAlis PRO. Agilent Technologies, Yarnton, Oxfordshire, England. Google Scholar
CambridgeSoft (2001). CHEMDRAW Ultra. CambridgeSoft Corporation, Cambridge, Massachusetts, USA. Google Scholar
Candia, M. de, Fiorella, F., Lopopolo, G., Carotti, A., Romano, M. R., Lograno, M. D., Martel, S., Carrupt, P.-A., Belviso, B. D., Caliandro, R. & Altomare, C. (2013). J. Med. Chem. 56, 8696–8711. Web of Science PubMed Google Scholar
El-Hiti, G. A. (2003). Monatsh. Chem. 134, 837–841. CAS Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Hodorowicz, M., Stadnicka, K., Trzewik, B. & Zaleska, B. (2007). Acta Cryst. E63, o4115. Web of Science CSD CrossRef IUCr Journals Google Scholar
Joule, J. A. & Mills, K. (2000). Heterocyclic Chemistry, 4th ed. England: Blackwell Science Publishers. Google Scholar
Koch, P., Schollmeyer, D. & Laufer, S. (2008). Acta Cryst. E64, o2216. Web of Science CSD CrossRef IUCr Journals Google Scholar
Liang, D., Gao, L.-X., Gao, Y., Xu, J. & Wang, W. (2008). Acta Cryst. E64, o201. Web of Science CSD CrossRef IUCr Journals Google Scholar
Mazik, M., Radunz, W. & Boese, R. (2004). J. Org. Chem. 69, 7448–7462. Web of Science CSD CrossRef PubMed CAS Google Scholar
Mazik, M. & Sicking, W. (2004). Tetrahedron Lett. 45, 3117–3121. Web of Science CSD CrossRef CAS Google Scholar
Seidler, T., Gryl, M., Trzewik, B. & Stadnicka, K. (2011). Acta Cryst. E67, o1507. Web of Science CSD CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Smith, K., Anderson, D. & Matthews, I. (1995). Sulfur Lett. 18, 79–95. CAS Google Scholar
Smith, K., El-Hiti, G. A. & Alshammari, M. B. (2013). Synthesis, 45, 3426–3434. Web of Science CrossRef CAS Google Scholar
Smith, K., El-Hiti, G. A., Fekri, A. & Alshammari, M. B. (2012). Heterocycles, 86, 391–410. Web of Science CrossRef CAS Google Scholar
Smith, K., El-Hiti, G. A., Pritchard, G. J. & Hamilton, A. (1999). J. Chem. Soc. Perkin Trans. 1, pp. 2299–2303. Web of Science CrossRef Google Scholar
Smith, K., Lindsay, C. M., Morris, I. K., Matthews, I. & Pritchard, G. J. (1994). Sulfur Lett. 17, 197–216. CAS Google Scholar
Thorat, S. A., Kang, D. W., Ryu, H. C., Kim, M. S., Kim, H. S., Ann, J., Ha, T., Kim, S.-E., Son, K., Choi, S., Blumberg, P. M., Frank, R., Bahrenberg, G., Schiene, K., Christoph, T. & Lee, J. (2013). Eur. J. Med. Chem. 64, 589–602. Web of Science CrossRef CAS PubMed Google Scholar
Turner, J. A. (1983). J. Org. Chem. 48, 3401–3408. CrossRef CAS Web of Science Google Scholar
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