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Amidation of a pyridine acylchloride with phenylglycine; N2,N6-bis((R)-carboxy(phenyl)methyl)pyridine-2,6-dicarboxamide

SyntheticPage 637
DOI: 10.1039/SP637
Submitted Jul 19, 2013, published Jul 22, 2013
Nikola P. Chmel (n.chmel@warwick.ac.uk), Pratik Gurnani (pratik.gurnani@warwick.ac.uk)
A contribution from Scott group, Warwick University


			Reaction Scheme: <img src="/images/empty.gif" alt="" />Amidation of a pyridine acylchloride with phenylglycine<img src="/images/empty.gif" alt="" />

Chemicals Used

(R)-2-Phenylglycine (Aldrich)
KOH
Pyridine-2,6-dicarbonyl dichloride (Prepared in house, see page 633)

Procedure

(R)-2-phenylglycine (1.53 g, 10.2 mmol) was suspended in water (25 ml) and solid KOH was added until the solution cleared. The mixture was chilled in an ice/water bath and pyridine-2,6-dicarbonyl chloride (1.04 g, 5.1 mmol) in DCM (25 ml) was added. The mixture was stirred for 0.5 h in an ice/water bath, then for another 0.5 h at ambient temperature. The DCM layer was discarded. The aqueous layer was diluted with a further 100 ml of water and was acidified with formic acid (6 ml of conc. HCOOH in 30 ml of water) until turbidity developed. The solution was left to crystallise overnight. The product was filtered, washed successively with water, ethanol and diethyl ether and dried in vacuo. The filtrate was concentrated to obtain the second crop. The combined product was recrystallised from methanol/water. Yield 0.55 g (25%).

Author's Comments

Make sure that the starting material chloride is clean. (see page 633)

Data

Elemental analysis found (calculated for C23H19N3O6∙3H2O) %: C 56.91 (56.67), H 5.17 (5.17), N 8.55 (8.62).

1H NMR (400 MHz, 298 K, CDCl3) δH 5.71 (s, 2H, CH), 7.31-7.43 (m, 6H, Ph-H), 7.54 (d, 4H, JHH=8Hz, Ph-H), 8.13 (t, 1H, JHH=8Hz, pyr), 8.26 (d, 2H, JHH=8Hz)

13C NMR (100 MHz, 298 K, CDCl3) δC 58.2 (CH), 126.4, 128.7, 129.5, 130.0 (Ph), 138.0, 140.7, 150.0 (pyr), 165.3 (C=O), 173.6 (COOH)

MS (ESI+) m/z 456.12 [(M+Na]+), 889.24 ([2M+Na]+)

IR (cm-1) ν 3391, 3036, 1725, 1669, 1513, 1442, 1389, 1319, 1253, 1182, 1095, 1074, 1030, 1001, 967, 843, 749, 724, 695, 663


Lead Reference

A. G. Talma, P. Jouin, J. G. De Vries, C. B. Troostwijk, G. H. W. Buning, J. K. Waninge, J. Visscher and R. M. Kellogg, J. Am. Chem. Soc., 1985, 107, 3981-3997.
http://dx.doi.org/10.1021/ja00299a038

Other References

Dalton Trans., 2011,40, 1722-1731 http://dx.doi.org/10.1039/c0dt01184c

Supplementary Information

Click to open interactive 1H NMR spectrum
Click to open interactive 13C NMR spectrum
1H NMR (1H NMR.jcamp)
13C NMR (13C NMR.jcamp)

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Keywords: acylation, acylchloride, addition, amines, elimination

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