NMR study of O and N, O-substituted 8-quinolinol derivatives Sobia Mastoor, a Shaheen Faizi, b * Rubeena Saleem a,c ** and Bina Shaheen Siddiqui b The 1 H and 13 C NMR spectral study of several biologically active derivatives of 8-quinolinol have been made through extensive NMR studies including homodecoupling and 2D-NMR experiments such as COSY-45°, NOESY, and HeteroCOSY. Electron donating resonance and electron withdrawing inductive effect of several groups showed marked changes in chemical shifts of nuclei at the seventh positions of O-substituted quinolinols (2–15). Although in N-alkyl, 8-alkoxyquinolinium halides (16–21), ring A rightly showed low frequency chemical shift values. Copyright © 2013 John Wiley & Sons, Ltd. Keywords: 8-quinolinol; NMR; 1 H; 13 C; COSY-45°; NOESY; HeteroCOSY; O-substituted quinolinol and N; O-dialkyl derivatives Introduction The 8-quinolinol (1), also known as oxine, is a powerful reagent. It is frequently used in synthesis of a variety of compounds, which are useful for chemical, biological, and industrial pur- poses. Oxine derivatives have been reported as a corrosion inhibitor, [1] in manufacturing dyes [2] and to detect metals. [3] Its 8-hydroxyquinolinato-bis-salicylato yttrium (III) complexes inhibits growth of Schizosaccharomyces pombe, [4] whereas lanthanide (III) complexes of 8-quinolinol Schiff bases are antioxidant and have the ability to bind DNA. [5] An aqueous solution of 8-quinolinol helps in quick germination of Eriobotrya japonica (loquat). [6] Recently, antimicrobial activity of oxine glucosaminides [7] and anti-inflammatory activity of 8-quinolinol Mannich bases [8] have been reported. Current work involves the NMR spectral study of various 8-quinolinol derivatives (2–21) possessing antimicrobial [9] and antiplatelet aggregating activities. [10] This is the first report of NMR data for compounds 6, 17–21 according to the Science Finder research engine (Fig. 1). [11] Experimental The 1 H and 13 C NMR spectra were recorded in CDCl 3 and DMSO-d 6 at 21–22 °C with Bruker Aspect AM-300 and AM-400 spec- trometers (Switzerland) working at 300 and 400 MHz for 1 H NMR and 75 and 100 MHz for 13 C NMR, respectively. For 1D (DEPT) and COSY-45° experiments, standard Bruker software was applied. In 1D measurements on AM-300 and AM-400 for 1 H and 13 C 32 K, data points were used for free induction decays. The digital reso- lutions were 0.122 and 0.164 Hz per point ( 1 H), 1.130 and 1.453 Hz per point ( 13 C) on AM-300 and AM-400, respectively. The spectral widths (in both CDCl 3 and DMSO-d 6 ) at 300 and 400 MHz were 4 and 5 KHz for 1 H NMR and 18 and 23 KHz for 13 C NMR at 75 and 100 MHz, respectively. The COSY-45° F 1 acquisition ranges between 377 and 4000 and that for F 2 recorded between 950 and 4000 Hz. Other COSY-45° parameters include 512 data points and 512 increments (both zero-filled to 1024), 1.5–2.0 s relaxation delay and 32 transients per increment. For 2D experiment, Bruker software library was used for the pulse program, [12] with the following parameters: for 300/75 and 400/100 MHz HeteroCOSY (AM-300 and AM-400), J ( 13 C, 1 H) = 140 Hz, data matrix 1 K × 2 K (256 experiments to 1 K zero filling in F 1, 2 K in F 2 ), 128 transients in each experiment. In NOESY, the mixing time is 0.9 s, the spectral width ranges from 1470 to 2551 Hz for F 2 and 735 to 1275 Hz for F 1 in both DMSO-d 6 and CDCl 3 . Data matrix 1 K × 2 K (256 experiments to 1 K zero filling in F 1 , 2 K in F 2 ), 64 transients in CDCl 3 and 16 in DMSO-d 6 . The delta values were referenced to DMSO-d 5 (2.50 and 39.7 ppm for 1 H and 13 C, respectively), and CHCl 3 (7.24 and 77.3 ppm for 1 H and 13 C, respectively) solvents. Exact assignment was made through 2D spectroscopy and literature values. [13,14] Preparation of O-alkyl (2–6) and N, O-dialkyl (16–20) derivatives In each experiment, 8-quinolinol (1, 2 g) and alkyl halide (2 ml) were added to a freshly prepared (15 ml) solution of sodium ethoxide and refluxed with stirring. The reaction mixture was monitored through TLC. Compounds 2 and 16 were formed after 2 hours while formation of 3–6 and 17–20 were completed after 2 days of reflux. The reaction mixture was poured into cold water and shaked with ethyl acetate. The ethyl acetate phase yielded monoalkyl derivatives, 8-methoxy * Correspondence to: Shaheen Faizi, International Center for Chemical and Bio- logical Sciences, University of Karachi, Karachi-76250, Pakistan. E-mail: shaheenfaizi@hotmail.com ** Correspondence to: Rubeena Saleem, Dr HMI Institute of Pharmacology & Herbal Sciences, Hamdard University, Karachi, 74600, Pakistan, Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi, 74600, Pakistan. E-mail: rs127pk@yahoo.com a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi, 74600, Pakistan b International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 76250, Pakistan c Dr HMI Institute of Pharmacology & Herbal Sciences, Hamdard University, Karachi, 74600, Pakistan Magn. Reson. Chem. 2014, 52, 115–121 Copyright © 2013 John Wiley & Sons, Ltd. MRC letters Received: 15 July 2013 Revised: 1 November 2013 Accepted: 5 November 2013 Published online in Wiley Online Library: 10 December 2013 (wileyonlinelibrary.com) DOI 10.1002/mrc.4034 115