One-bond and long-range coupling constants of substituted 2-cyanopyridines. GIAO/DFT calculations of proton and carbon chemical shifts and coupling constants Alan R. Katritzky a, * , Novruz G. Akhmedov a , Ala ˆattin Gu ¨ven b , Eric F.V. Scriven a , Suman Majumder a , Rena G. Akhmedova a , C. Dennis Hall a a Department of Chemistry, Center for Heterocyclic Compounds, University of Florida, P.O. Box 117200, Gainesville, FL 32611-7200, USA b Department of Chemistry, Faculty of Science, Anadolu University, 26470 Eskisehir, Turkey Received 7 January 2005; revised 2 July 2005; accepted 7 July 2005 Available online 20 October 2005 Abstract The magnitude of one bond and long-range coupling constants ( n J HH and n J CH ) in isomeric cyanopyridines-(1, 2, 3), methyl-(4, 5, 6, 7), 3-ethyl-(8), chloro-(9), 3-bromo-(10), acetyl-(11, 12), 5-ethoxycarbonyl-(13) and 4-(4 0 -pyridyl)-(14) derivatives of 2-cyanopyridines were determined in CDCl 3 . The Density Functional Theory/Gauge Including Atomic Orbitals (GIAO/DFT) calculation was employed for the estimation of proton or carbon chemical shifts and coupling constants ( n J HH and n J CH ) and the calculated NMR data compared with the experimental NMR data. The experimental values of n J HH and n J CH in derivatives of 2-cyanopyridines 1–14 are discussed with respect to the corresponding data in previously reported compounds and compared with values obtained from GIAO/DFT calculations and iterative simulation using gNMR software. Assignments of proton and carbon chemical shifts were achieved using one- and two-dimensional NMR techniques, such as 1D NOE difference, COSY, long-range COSY, gHMBC and gHMQC. q 2005 Elsevier B.V. All rights reserved. Keywords: Long-range coupling constants; GIAO; 2-Cyanopyridines; Proton-coupled 13 C NMR spectra 1. Introduction Pyridine and derivatives have been the subject of extensive experimental [1–20] and theoretical NMR studies [21–34]. The electronegative nitrogen atom in the pyridine ring results in the 1 H NMR spectra of protons in the a-position of the pyridine ring appearing at low field relative to those in the b- and g-positions. As a consequence, the 1 H NMR spectra of pyridines are often readily analyzed on a first-order basis in order to derive chemical shifts and coupling constants. The vicinal ( 3 J HH ) couplings fall into two ranges: J ab generally lies in the range 4.5–5.0 Hz, whereas J bg at 7.0–9.2 Hz is more typical of substituted benzenes [35–36]. It has been suggested that the reason for the low value of 3 J ab in pyridine and the corresponding increase of coupling in pyridinium ions and N-oxides arises from electronegativity effects and C–H bond polarization [37]. Cyano-derivatives of pyridine have also been the subject of considerable interest. Compounds containing the pyr- idinecarbonitrile moiety possess fluorescent and mechanical properties and have been used in the treatment of paper [38]. Moreover, substituted cyanopyridines exhibit antimicrobial [39] and antihistaminic [40] activity. The structures of isomeric pyridines 1–3 have been studied by low-temperature X-ray [41] crystallography and by methods such as microwave [42] and surface enhanced Raman spectroscopy [43]. The 13 C NMR data (chemical shifts and carbon–proton coupling constants) of 2-, 3- and 4-cyanopyridines and also methyl-substituted pyridines have been published by Yoshito [44]. However, the long-range cyano ( n J CN,H , nZ3, 4) coupling constants were reported incompletely and with a low level of precision. More recently, Denisov and co-workers [28,29] investigated the proton-coupled 13 C NMR spectra (at 50 MHz) of isomeric cyanopyridnes 1–3. Journal of Molecular Structure 783 (2006) 191–203 www.elsevier.com/locate/molstruc 0022-2860/$ - see front matter q 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2005.07.003 * Corresponding author. Tel.: C1 352 392 0554; fax: C1 352 392 9199. E-mail address: katritzky@chem.ufl.edu (A.R. Katritzky).