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
NMR study of O and N, O-substituted 8-quinolinol derivatives Sobia Mastoor,a Shaheen Faizi,b* Rubeena Saleema,c** and Bina Shaheen Siddiquib The 1H and 13C 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; 1H;
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 purposes. 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
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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 Biological Sciences, University of Karachi, Karachi-76250, Pakistan. E-mail: [email protected] ** 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: [email protected] 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
Copyright © 2013 John Wiley & Sons, Ltd.
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The 1H and 13C NMR spectra were recorded in CDCl3 and DMSO-d6 at 21–22 °C with Bruker Aspect AM-300 and AM-400 spectrometers (Switzerland) working at 300 and 400 MHz for 1H NMR and 75 and 100 MHz for 13C NMR, respectively. For 1D (DEPT) and COSY-45° experiments, standard Bruker software was applied. In 1D measurements on AM-300 and AM-400 for 1H and 13C 32 K, data points were used for free induction decays. The digital resolutions were 0.122 and 0.164 Hz per point (1H), 1.130 and 1.453 Hz per point (13C) on AM-300 and AM-400, respectively. The spectral widths (in both CDCl3 and DMSO-d6) at 300 and 400 MHz were 4 and 5 KHz for 1H NMR and 18 and 23 KHz for 13C NMR at 75 and 100 MHz, respectively. The COSY-45° F1 acquisition ranges between 377 and 4000 and that for F2 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 (13C, 1H) = 140 Hz, data matrix 1 K × 2 K (256 experiments to 1 K zero filling in F1, 2 K in F2), 128 transients in each experiment. In NOESY, the mixing time is 0.9 s, the spectral width ranges from 1470 to 2551 Hz for F2 and 735 to 1275 Hz for F1 in both DMSO-d6 and CDCl3. Data matrix 1 K × 2 K (256 experiments to 1 K zero filling in F1, 2 K in F2), 64 transients in CDCl3 and 16 in DMSO-d6. The delta values were referenced to DMSO-d5 (2.50 and 39.7 ppm for 1H and 13C, respectively), and CHCl3 (7.24 and 77.3 ppm for 1H and 13C, respectively) solvents. Exact assignment was made through 2D spectroscopy and literature values.[13,14]
S. Mastoor et al.
Figure 1. Structures 1-21.
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quinoline (2, 85 mg), 8-ethyoxy quinoline (3, 94 mg), 8-propyloxy quinoline (4, 1.0 g), 8-butyloxy quinoline (5, 1.0 g), and 8-pentyloxy quinoline (6, 1.2 g). Whereas aqueous phase after freeze drying and thin-layer chromatography (silica gel, CHCl3–CH3OH, 9.5 : 0.5) yielded dialkyl derivatives, N-methyl, 8-methoxy quinolinium iodide (16, 2.1 g); N-ethyl, 8-ethoxy quinolinium iodide (17, 2.2 g), yellow irregular plates, melting point (mp) 170–172 °C; N-propyl, 8-propyloxy quinolinium bromide (18, 1.0 g) needles, mp 130–132 °C; N-butyl, 8-butyloxy quinolinium bromide (19, 1.9 g); and N-pentyl, 8-pentyloxy quinolinium bromide (20, 2.3 g).
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Preparation of benzyloxy (7) and N, O-dibenzyl (21) derivatives Sodium hydroxide (1.0 g) and benzyl chloride (3 ml) were added to a solution of 8-quinolinol (1, 2.0 g) in dimethyl sulfoxide (4.0 ml) and kept under normal conditions of temperature and pressure for 2 days. On usual workup of reaction mixture (as mentioned for 2–6 and 16–21), the ethyl acetate phase yielded 8-benzyloxy quinoline (7, 1.0 g). The aqueous phase was neutralized and freeze dried. The thick mass obtained was purified by thin-layer chromatography (silica gel, CHCl3:CH3OH,
Copyright © 2013 John Wiley & Sons, Ltd.
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Copyright © 2013 John Wiley & Sons, Ltd.
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8.77 dd (4.2, 1.5) 7.35 dd (8.3, 4.2) 8.08 dd (8.3, 1.5) 7.29 dd (8.2, 1.1) 7.44 dd (8.2, 7.5) 7.22 dd (7.5, 1.1) — — — — — — — — —
1
8.81 dd (4.1, 1.5) 7.50 dd (8.3, 4.1) 8.27 dd (8.3, 1.5) 7.36 dd (8.1, 1.3) 7.41 dd (8.1, 7.4) 7.08 dd (7.4, 1.3) — — — — — — — — —
1a 8.90 dd (4.2, 1.7) 7.39 dd (8.3, 4.2) 8.09 dd (8.3, 1.8) 7.35 dd (8.3, 1.3) 7.43 dd (8.3, 7.6) 7.02 dd (7.6, 1.3) 4.06 s — — — — — — — —
2
Coupling constants are given in parentheses. Solvent (CD3)2SO; 1* OH δ 9.76 s.
a
H-1′ H-2′ H-3′ H-3′ (a) H-3′ (b) H-4′ H-5′ H-6′ H-7′
H-7
H-6
H-5
H-4
H-3
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H-2
Proton
1
8.89 dd (4.2, 1.7) 7.32 dd (8.3, 4.2) 8.02 dd (8.3, 1.7) 7.28 dd (8.2, 1.2) 7.35 dd (8.2, 7.7) 6.96 dd (7.7, 1.2) 4.23 q (7.0) 1.54 t (7.0) — — — — — — —
3 8.88 dd (4.2, 1.8) 7.32 dd (8.3, 4.2) 8.01 dd (8.3, 1.8) 7.33 dd (8.3, 1.0) 7.36 dd (8.3, 8.2) 6.97 br.d (8.2) 4.12 t (7.5) 1.97 (7.5) 1.04 t (7.5) — — — — — —
4
Table 1. The H NMR chemical shifts and their multiplicities for derivatives 1–8 in CDCl3
8.91 dd (4.1, 1.6) 7.36 dd (8.3, 4.1) 8.07 dd (8.2, 1.6) 7.32 dd (8.0, 1.0) 7.40 dd (8.0, 7.6) 7.02 dd (7.6, 1.0) 4.21 t (7.2) 1.98 quin. (7.2) 1.55 (7.2) — — 0.98 t (7.2) — — —
5 8.90 dd (4.2, 1.7) 7.34 dd (8.3, 4.2) 8.03 dd (8.3, 1.7) 7.30 dd (7.2, 1.1) 7.38 dd (7.5, 7.2) 7.00 br.d (7.5) 4.18 t (7.3) 1.99 quin. (7.3) 1.46 quin. (7.2) — — 1.43 (7.3) 0.90 t (7.3) — —
6
— 7.17 d (7.0) 7.38 m — — 7.17 m 7.38 m 7.17 d (7.0) 5.29 s
8.86 dd (4.2, 1.2) 7.38 m — 8.11 dd (8.3, 1.2) 7.20 m — 7.30 m — 6.99 m
7 8.86 dd (4.1, 1.6) 7.55 dd (8.3, 4.1) 8.34 dd (8.3, 1.6) 7.51 dd (6.8, 2.1) 7.52 dd (6.8, 6.6) 7.29 dd (6.6, 2.1) — 7.27 dd (7.3, 1.6) 7.38 dd (7.3, 7.0) — — 7.53 br.t(7.0) 7.38 dd (7.3, 7.0) 7.27 dd (7.3, 1.6) 5.30 s
7a
4.83 td (5.8, 1.5) 6.18 tdd (17.3, 10.5, 5.8) — 5.43 tdd (17.3, 1.5, 1.5) 5.29 tdd (10.5, 1.5, 1.5) — — — —
8.91 dd (4.2, 1.8) — 7.36 m — 8.07 dd (8.3, 1.8) — 7.37 m — 7.39 m — 7.03 dd (7.3, 1.7)
8
NMR of 8-quinolinol
8.75 dd (4.2, 1.7) 7.35 dd (8.3, 4.2) 8.10 dd (8.3, 1.7) 7.72 dd (8.1, 1.4) 7.46 dd (8.1, 7.6) 7.59 dd (7.6, 1.4) 7.96 dd (8.4, 1.4) 7.43 dd (8.4, 7.6) 7.45 tt (7.6, 1.4) 7.43 dd (8.4, 7.6) 7.69 dd (8.4, 1.4) — — 8.87 dd (4.1, 1.7) 7.57 dd (8.3, 4.1) 8.41 dd (8.3, 1.7) 7.90 dd (8.1, 1.4) 7.61 dd (8.1, 7.4) 7.53 dd (7.4, 1.4) 6.27 qd (15.5, 1.7) 7.17 qd (15.5, 6.9) 1.98 dd (6.9, 1.7) — — — —
8.80 dd (4.2, 1.7) 7.36 dd (8.3, 4.2) 8.10 dd (8.3, 1.7) 7.71 dd (8.1, 1.4) 7.47 dd (8.1, 7.6) 7.59 dd (7.6, 1.4) 7.86 d (8.4) 7.23 dd (8.4, 0.7) — 7.23 dd (8.4, 0.7) 7.86 d (8.4) — —
9.5 : 0.5) that furnished N-benzyl, 8-benzyloxy quinolinium chloride (21, 2.0 g), rods, mp 145–147 °C. Preparation of allyloxy (8), p-nitrobenzyloxy (9), and crotonyloxy (13) derivatives For each experiment, a solution of 8-quinolinol (1, 2.0 g) was dissolved in acetone (15 ml) to which potassium carbonate and the corresponding alkyl halides [allyl bromide (2.0 ml), p-nitrobenzyl chloride (2.3 g) and crotonyl chloride (2.0 ml)] were added and the reaction mixture was refluxed with stirring. Compounds 8, 9, and 10 were formed after 3 h, 2 days, and 5 h, respectively, as revealed by TLC. On usual workup of reaction mixture, the ethyl acetate phase of the respective reaction mixture, yielded pure 8-allyloxy quinoline (8, 1.9 g); 8-p-nitrobenzyloxy quinoline (9, 3.0 g) and 8-crotonyloxy quinoline (13, 2.2 g), irregular plates, mp 98–100 °C. Preparation of acetyloxy (10), benzoyloxy (11), cinnamoyloxy (12), benzene sulfonyloxy (14), and p-toluene sulfonyloxy (15) derivatives
Results and Discussion
Coupling constants are given in parentheses. Solvent (CD3)2SO; 9 H-7′ δ 5.49 s, 15 4′-CH3 δ 2.39 br. s.
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In each experiment, to a solution of 8-quinolinol (1, 2.0 g) in pyridine (2.0 ml) acetic anhydride (2.0 ml), benzoyl chloride (2.0 ml), benzene sulfonyl chloride (2.0 ml), p-toluene sulfonyl chloride (3.0 g), and cinnamoyl chloride (3.0 g) were added and kept at room temperature for 2 h (10), 4 h (11), 10 days (12), and 1 day (14) and (15). On usual workup, organic phase yielded 8-acetoxy quinoline (10, 1.8 g), 8-benzoyloxy quinoline (11, 2.8 g), prismatic rods, mp 120–123 °C; 8-cinnamoyloxy quinoline (12, 3.0 g), irregular transparent plates, mp 63–65 °C; 8-benzene sulfonyloxy quinoline (14, 2.4 g), semicrystalline, mp 176–178 °C, and 8-p-toluene sulfonyloxy quinoline (15, 2.8 g), cylindrical rods, mp 115–117 °C.
a
8.89 dd (4.2, 1.6) 7.58 dd (8.3, 4.2) 8.44 dd (8.3, 1.6) 7.92 dd (7.6, 2.0) 7.65 dd (8.0, 7.6) 7.61 dd (8.0, 2.0) 7.83 dd (7.3, 2.2) 7.47 m 7.47 m 7.47 m 7.83 dd (7.3, 2.2) 7.03d (16.1) 7.91d (16.1) 8.94 dd (4.2, 1.8) 7.42 dd (8.3, 4.2) 8.11 dd (8.3, 1.8) 7.39 dd (8.3, 1.6) 7.35dd (8.3, 7.3) 6.97dd (7.3, 1.6) 7.67 dd (8.5, 0.69) 8.17 d (8.5) — 8.17 d (8.5) 7.67 dd (8.5, 0.69) — — H-2 H-3 H-4 H-5 H-6 H-7 H-2′ H-3′ H-4′ H-5′ H-6′ α CH β CH
8.80 dd (4.2, 1.6) 7.17 dd (8.3, 4.2) 7.91 dd (8.3, 1.6) 7.49 m 7.33 m 7.33 m 2.41 s — — — — — —
9.00 dd (4.5, 1.5) 7.74 dd (8.4, 4.5) 8.75 dd (8.4, 1.5) 8.08 dd (8.1, 1.3) 7.76 dd (8.1, 7.6) 7.48 dd (7.6, 1.3) 8.22 dd (8.3, 1.3) 7.62 dd (8.3, 7.3) 7.77 tt (7.3, 1.3) 7.62 dd (8.3, 7.3) 8.22 dd (8.3, 1.3) — —
8.87 dd (4.2, 1.6) 7.32 dd (8.3, 4.2) 8.08 dd (8.3, 1.6) 7.65 m 7.47 m 7.47 m 7.55 m 7.35 m 7.35 m 7.35 m 7.55 m 6.85d (15.9) 7.59d (15.9)
8.87 dd (4.2, 1.7) 7.31 dd (8.3, 4.2) 8.06 dd (8.3, 1.7) 7.62 m 7.49 m 7.43 m 6.25qd (15.5, 1.7) 7.27 qd (8.5) 1.93 dd (6.9, 1.7) — — — —
14 12a 12 11a 10 9 Proton
1
Table 2. The H NMR chemical shifts and their multiplicities for derivatives 9–15 in CDCl3
13
13a
15
S. Mastoor et al.
NMR study of 8-quinolinol (1) showed six doublet of doublets at δ 8.77 (J2,3 4.2 Hz, J2,4 1.5 Hz, H-2), δ 7.35 (J3,4 8.3 Hz, J3,2 4.2 Hz, H-3), δ 8.08 (J4,3 8.3 Hz, J4,2 1.5 Hz, H-4), δ 7.29 (J5,6 8.2 Hz, J5,7 1.1 Hz, H-5), δ 7.44 (J6,5 8.2 Hz, J6,7 7.5 Hz, H-6), and δ 7.22 (J7,6 7.5 Hz, J7,5 1.1 Hz, H-7). Signal for OH at C-8 was not observed in CDCl3 but in DMSO-d6 appeared at δ 9.76 (Table 1). The proton signals were assigned on the basis of chemical shift arguments and coupling patterns. These assignments were transferred to C-2 to C-7 through HeteroCOSY, whereas that for quaternary carbons was made through 13C NMR and literature.[14] Nucleophilic substitution reaction of 8-quinolinol with different reagents produced several 8-O-substituted derivatives (2–15) and N-alkyl, 8-alkoxy quinolinium halides (16–21). It is worth mentioning that multiplicities in 8-benzyloxy quinoline (7), 8-cinnamoyloxy (12), and 8-crotonyloxy (13) were better resolved in DMSO-d6 (Tables 1–4). Electron withdrawing effect of substituents in compounds 9–15 was more pronouncedly observed in 13C NMR (Table 5) than 1H NMR (Table 2). 8-Acetyloxy quinoline (10) was found to be unstable and promptly hydrolyzed to 8-quinolinol as observed earlier.[15] This is due to the intramolecular neighboring effect of quinoline nitrogen.[15] Among N, O-substituted dialkyl quinolinium halides (16–21), both hydrogen and carbon nuclei showed high frequency chemical shift values as compared with 8-quinolinol (Tables 3 and 6). However, ring A nuclei displayed higher desheilding effects because of the presence of the positive charge on quinoline nitrogen (Tables 3 and 6).
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10.02 dd (5.8, 0.7) 8.09 dd (8.4, 5.8) 8.98 dd (8.4, 0.7) 7.83 m 7.83 m 7.53 dd (6.6, 2.7) 4.12 s — — — — — 5.03 s — — — — —
16
a
16a 9.31 dd (5.8, 1.2) 8.08 dd (8.4, 5.8) 9.17 dd (8.4, 1.2) 7.96 dd (8.1, 1.6) 7.92 dd (8.1, 7.7) 7.76 dd (7.7, 1.6) 4.07 s — — — — — 4.78 s — — — — —
Coupling constants are given in parentheses. Solvent (CD3)2SO; 21 H-7′ δ 5.31 s, H-7″ δ 6.55 s.
H-2 H-3 H-4 H-5 H-6 H-7 H-1′ H-2′ H-3′ H-4′ H-5′ H-6′ H-1″ H-2″ H-3″ H-4″ H-5″ H-6″
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Proton
1
9.93 dd (5.7, 1.2) 8.04 dd (8.4, 5.7) 9.06 dd (8.4, 1.2) 7.85 dd (8.1, 1.1) 7.79 dd (8.1, 7.9) 7.57 br.d (7.9) 4.32 q (7.0) 1.53 t (7.0) — — — — 5.47 q (7.1) 1.65 t (7.1) — — — —
17
Table 3. The H NMR chemical shifts and their multiplicities for derivatives 16–21 in CDCl3
9.57 dd (5.8, 1.4) 8.71 dd (8.4, 5.8) 9.28 dd (8.4, 1.4) 8.02 dd (8.2, 1.4) 7.91 dd (8.2, 8.0) 7.81 dd (8.0, 1.4) 4.27 t (6.6) 1.91 m 0.91 t (7.4) — — — 5.20 t (7.8) 1.96 m 1.04 t (7.4) — — —
18a 10.25 br.d (5.20) 8.15 dd (8.0, 5.2) 9.02 br.d (8.0) 7.81 m 7.81 m 7.54 br.d (7.52) 4.27 t (6.6) 1.94 m 1.45 m 0.94 t (7.4) — — 5.54 t (7.6) 1.94 m 1.53 m 1.00 t (7.4) — —
19a
9.53 dd (5.8, 1.1) 8.13 dd (8.3, 5.8) 9.26 dd (8.3, 1.1) 8.01 dd (7.9, 1.3) 7.92 t (7.9) 7.84 dd (7.9, 1.3) 4.32 t (6.6) 1.92 m 1.46 m 1.33 m 0.86 t (7.1) — 5.23 t (7.7) 1.96 m 1.50 m 1.39 m 0.91 t (7.2) —
20a
9.70 dd (5.8, 1.0) 8.25 dd (8.3, 5.8) 9.38 br.d (8.3) 8.06br.d (8.1) 7.90 dd (8.1, 8.0) 7.78 br.d (8.0) — 6.82 dd (6.5, 1.5) 7.21 m 7.21 m 7.21 m 6.82 dd (6.5, 1.5) — 7.32 m 7.21 m 7.21 m 7.21 m 7.32 m
21
NMR of 8-quinolinol
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13
147.89 121.68 136.10 117.85 127.68 110.23 152.36 138.30 128.55 — — — — — —
1
Copyright © 2013 John Wiley & Sons, Ltd.
13
149.29 121.59 135.77 120.53 126.24 110.02 153.56 140.21 132.40 144.32 127.34 123.65 147.32 123.65 127.34
9 150.47 121.68 136.20 125.97 126.25 121.77 147.38 141.15 129.58 169.83 21.02 — — — —
10
C NMR chemical shifts (δ) for derivatives 9–15 in CDCl3
149.04 121.74 136.41 119.58 126.97 107.85 155.26 139.77 129.45 56.03 — — — — —
2
154.37 139.43 145.88 131.98 127.77 129.34 150.03 142.08 134.52 134.05 135.53 134.19 133.08 134.19 135.53
11a
148.95 121.29 135.82 119.16 126.50 108.34 154.44 138.13 129.28 64.08 14.51 — — — —
3
150.35 121.60 136.08 125.75 126.20 121.60 147.34 141.16 129.51 134.33 128.31 128.87 130.50 128.87 128.87
12
a
Solvent (CD3)2SO; 9 C-7′ δ 69.47, 11* OCO δ 169.99, 12 OCO δ 165.48, αCH δ 117.23, βCH δ 146.83, 15 4′-CH3 δ 21.65.
C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ C-4′ C-5′ C-6′
Carbon
Table 5. The
a
148.14 121.82 136.04 117.71 127.49 111.26 153.32 138.50 128.80 — — — — — —
1a
C NMR chemical shifts (δ) for derivatives 1–4, 6–8 in CDCl3
Solvent (CD3)2SO; 7 C-7′ δ 70.82.
C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ C-4′ C-5′ C-6′
Carbon
Table 4. The
149.04 121.29 135.66 119.16 126.48 108.47 154.70 140.25 129.31 70.22 22.06 10.30 — — —
4
150.41 121.48 135.88 125.68 126.07 121.52 147.29 141.29 129.41 164.83 121.85 147.23 18.08 — —
13
149.31 121.53 135.93 119.37 126.74 108.68 154.97 140.49 129.56 69.03 28.71 28.21 22.53 14.01 —
6
150.79 121.94 135.91 127.16 126.12 122.73 145.49 136.20 129.69 141.58 128.86 128.83 134.03 128.83 128.86
14
148.86 121.70 136.77 119.99 126.94 110.26 153.95 139.65 128.32 130.59 128.62 127.33 127.92 127.33 128.62
7
150.69 121.83 135.80 125.99 126.97 122.46 145.50 133.22 129.63 145 128.75 129.63 141.48 129.63 128.75
15
148.99 121.29 135.4 119.50 126.54 109.13 154.07 140.19 129.24 69.59 132.95 117.95 — — —
8
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Magn. Reson. Chem. 2014, 52, 115–121
NMR of 8-quinolinol Table 6. The
13
C NMR chemical shifts (δ) for derivatives 16–21 in (CD3)2SO
Carbon C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ C-4′ C-5′ C-6′ C-1″ C-2″ C-3″ C-4″ C-5″ C-6″ a
16a
17a
18
19
20
21
152.40 122.98 147.12 122.55 130.82 115.94 151.63 132.11 130.82 57.42 — — — — — 53.16 — — — — —
151.32 122.93 147.63 122.87 130.90 116.93 149.94 132.44 129.43 66.72 14.46 — — — — 59.69 18.25 — — — —
151.64 122.53 147.76 122.30 130.42 117.28 150.94 132.18 129.09 72.18 21.84 10.29 — — — 64.07 25.21 10.67 — — —
152.56 122.87 147.20 122.87 130.45 116.42 150.23 132.41 129.30 70.68 30.83 19.37 13.63 — — 63.53 34.77 19.37 13.68 — —
151.52 122.27 147.67 122.49 130.34 117.16 149.78 132.13 129.08 70.57 28.09 27.73 21.82 13.76 — 62.76 31.67 27.80 21.86 13.76 —
152.96 123.39 149.27 123.08 131.18 118.31 149.60 136.51 130.10 132.90 126.12 128.84 129.49 128.84 126.12 136.51 128.84 129.23 129.49 129.23 128.84
Solvent CDCl3; 21 C-7′ δ 72.12, C-7″ δ 65.73.
Acknowledgement The authors thankfully acknowledge the help and cooperation of Dr Muhammad Ali Versani, Associate Professor at Federal Urdu University, Karachi, Pakistan, for explaining the instrumental details.
References [1] R. F. Zhang, S. F. Zhang, N. Yang, L. J. Yao, F. X. He, Y. P. Zhou, X. Xu, L. Chang, S. J. Bai. J. Alloys Compd. 2012, 539, 249–255. [2] M. Sacmaci, H. K. Cavus, H. Ari, R. Sahingöz, T. Özpozan. Spectrochim. Acta Mol. Biomol. spectros. Part A 2012, 97, 88–99. [3] A. Fuentes-Cid, J. Villanueva-Alonso, E. Pena-Vazquez, P. BermejoBarrera. Anal. Chim. Acta 2012, 749, 36–43. [4] L. Xu, L. Qiang-Guo, Z. Hui, H. Ji-Lin, Y. Fei-Hong, Y. De-Jun, X. Sheng-Xiong, Y. Li-Juan, H. Yi, G. Dong-Cai. Biol. Trace Elem. Res. 2012, 147, 366–373. [5] Y. Liu, K. Zhang, Y. Wu, J. Zhao, J. Liu. Chem. Biodiv. 2012, 9, 1533–1544.
[6] L. Guolu, G. Qigao, W. Weixing, L. Xiolin, X. Suqiong, H. Qiao, L. Yanmei, S. Haiyan. Faming Zhuanli Shenqing 2012, 9. [7] T. A. Chupakhina, A. M. Katsev, V. O. Kur´yanov. Russ. J. Bioorg. Chem. 2012, 38, 422–427. [8] G. Krishnamoorthy, M. I. F. Mohamed. Indian J. Het. Chem. 2012, 21(4), 383–384. [9] K. A. Khan, S. A. Khan, S. M. Khalid, A. Ahmed, B. S. Siddiqui, R. Saleem, S. Siddiqui, S. Faizi. Arzneim.-Forsch. Drug Res 1994, 44, 972–975. [10] S. A. Saeed, R. U. Simjee, A. S. Gilani, S. Siddiqui, R. Saleem, S. Faizi, B. S. Siddiqui, S. Farnaz. Biochem. Soc. Trans. 1992, 20, 357. [11] http://www.sci.finder.cas.org.com. [26 February 2013] [12] G. E. Martin, A. S. Zektzer, Two-dimensional NMR Methods for Establishing Molecular Connectivty, VCH, New York, 1988. [13] W. Brugel, Handbook of NMR Spectral Parameters, Heyden & Son Ltd., London, 1979, pp. 612. [14] A. W. K. Khanzada, M. A. Chippa, M. I. Bhanger, G. H. Kazi. J. Chem. Soc. Pak. 1989, 11, 256–261. [15] S. M. Felton, T. C. Bruice. J. Am. Chem. Soc. 1969, 91, 6721–6732.
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Revised: 1 November 2013
Accepted: 5 November 2013
Published online in Wiley Online Library: 10 December 2013
(wileyonlinelibrary.com) DOI 10.1002/mrc.4034
NMR study of O and N, O-substituted 8-quinolinol derivatives Sobia Mastoor,a Shaheen Faizi,b* Rubeena Saleema,c** and Bina Shaheen Siddiquib The 1H and 13C 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; 1H;
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 purposes. 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
Magn. Reson. Chem. 2014, 52, 115–121
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 Biological Sciences, University of Karachi, Karachi-76250, Pakistan. E-mail: [email protected] ** 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: [email protected] 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
Copyright © 2013 John Wiley & Sons, Ltd.
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The 1H and 13C NMR spectra were recorded in CDCl3 and DMSO-d6 at 21–22 °C with Bruker Aspect AM-300 and AM-400 spectrometers (Switzerland) working at 300 and 400 MHz for 1H NMR and 75 and 100 MHz for 13C NMR, respectively. For 1D (DEPT) and COSY-45° experiments, standard Bruker software was applied. In 1D measurements on AM-300 and AM-400 for 1H and 13C 32 K, data points were used for free induction decays. The digital resolutions were 0.122 and 0.164 Hz per point (1H), 1.130 and 1.453 Hz per point (13C) on AM-300 and AM-400, respectively. The spectral widths (in both CDCl3 and DMSO-d6) at 300 and 400 MHz were 4 and 5 KHz for 1H NMR and 18 and 23 KHz for 13C NMR at 75 and 100 MHz, respectively. The COSY-45° F1 acquisition ranges between 377 and 4000 and that for F2 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 (13C, 1H) = 140 Hz, data matrix 1 K × 2 K (256 experiments to 1 K zero filling in F1, 2 K in F2), 128 transients in each experiment. In NOESY, the mixing time is 0.9 s, the spectral width ranges from 1470 to 2551 Hz for F2 and 735 to 1275 Hz for F1 in both DMSO-d6 and CDCl3. Data matrix 1 K × 2 K (256 experiments to 1 K zero filling in F1, 2 K in F2), 64 transients in CDCl3 and 16 in DMSO-d6. The delta values were referenced to DMSO-d5 (2.50 and 39.7 ppm for 1H and 13C, respectively), and CHCl3 (7.24 and 77.3 ppm for 1H and 13C, respectively) solvents. Exact assignment was made through 2D spectroscopy and literature values.[13,14]
S. Mastoor et al.
Figure 1. Structures 1-21.
116
quinoline (2, 85 mg), 8-ethyoxy quinoline (3, 94 mg), 8-propyloxy quinoline (4, 1.0 g), 8-butyloxy quinoline (5, 1.0 g), and 8-pentyloxy quinoline (6, 1.2 g). Whereas aqueous phase after freeze drying and thin-layer chromatography (silica gel, CHCl3–CH3OH, 9.5 : 0.5) yielded dialkyl derivatives, N-methyl, 8-methoxy quinolinium iodide (16, 2.1 g); N-ethyl, 8-ethoxy quinolinium iodide (17, 2.2 g), yellow irregular plates, melting point (mp) 170–172 °C; N-propyl, 8-propyloxy quinolinium bromide (18, 1.0 g) needles, mp 130–132 °C; N-butyl, 8-butyloxy quinolinium bromide (19, 1.9 g); and N-pentyl, 8-pentyloxy quinolinium bromide (20, 2.3 g).
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Preparation of benzyloxy (7) and N, O-dibenzyl (21) derivatives Sodium hydroxide (1.0 g) and benzyl chloride (3 ml) were added to a solution of 8-quinolinol (1, 2.0 g) in dimethyl sulfoxide (4.0 ml) and kept under normal conditions of temperature and pressure for 2 days. On usual workup of reaction mixture (as mentioned for 2–6 and 16–21), the ethyl acetate phase yielded 8-benzyloxy quinoline (7, 1.0 g). The aqueous phase was neutralized and freeze dried. The thick mass obtained was purified by thin-layer chromatography (silica gel, CHCl3:CH3OH,
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8.77 dd (4.2, 1.5) 7.35 dd (8.3, 4.2) 8.08 dd (8.3, 1.5) 7.29 dd (8.2, 1.1) 7.44 dd (8.2, 7.5) 7.22 dd (7.5, 1.1) — — — — — — — — —
1
8.81 dd (4.1, 1.5) 7.50 dd (8.3, 4.1) 8.27 dd (8.3, 1.5) 7.36 dd (8.1, 1.3) 7.41 dd (8.1, 7.4) 7.08 dd (7.4, 1.3) — — — — — — — — —
1a 8.90 dd (4.2, 1.7) 7.39 dd (8.3, 4.2) 8.09 dd (8.3, 1.8) 7.35 dd (8.3, 1.3) 7.43 dd (8.3, 7.6) 7.02 dd (7.6, 1.3) 4.06 s — — — — — — — —
2
Coupling constants are given in parentheses. Solvent (CD3)2SO; 1* OH δ 9.76 s.
a
H-1′ H-2′ H-3′ H-3′ (a) H-3′ (b) H-4′ H-5′ H-6′ H-7′
H-7
H-6
H-5
H-4
H-3
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H-2
Proton
1
8.89 dd (4.2, 1.7) 7.32 dd (8.3, 4.2) 8.02 dd (8.3, 1.7) 7.28 dd (8.2, 1.2) 7.35 dd (8.2, 7.7) 6.96 dd (7.7, 1.2) 4.23 q (7.0) 1.54 t (7.0) — — — — — — —
3 8.88 dd (4.2, 1.8) 7.32 dd (8.3, 4.2) 8.01 dd (8.3, 1.8) 7.33 dd (8.3, 1.0) 7.36 dd (8.3, 8.2) 6.97 br.d (8.2) 4.12 t (7.5) 1.97 (7.5) 1.04 t (7.5) — — — — — —
4
Table 1. The H NMR chemical shifts and their multiplicities for derivatives 1–8 in CDCl3
8.91 dd (4.1, 1.6) 7.36 dd (8.3, 4.1) 8.07 dd (8.2, 1.6) 7.32 dd (8.0, 1.0) 7.40 dd (8.0, 7.6) 7.02 dd (7.6, 1.0) 4.21 t (7.2) 1.98 quin. (7.2) 1.55 (7.2) — — 0.98 t (7.2) — — —
5 8.90 dd (4.2, 1.7) 7.34 dd (8.3, 4.2) 8.03 dd (8.3, 1.7) 7.30 dd (7.2, 1.1) 7.38 dd (7.5, 7.2) 7.00 br.d (7.5) 4.18 t (7.3) 1.99 quin. (7.3) 1.46 quin. (7.2) — — 1.43 (7.3) 0.90 t (7.3) — —
6
— 7.17 d (7.0) 7.38 m — — 7.17 m 7.38 m 7.17 d (7.0) 5.29 s
8.86 dd (4.2, 1.2) 7.38 m — 8.11 dd (8.3, 1.2) 7.20 m — 7.30 m — 6.99 m
7 8.86 dd (4.1, 1.6) 7.55 dd (8.3, 4.1) 8.34 dd (8.3, 1.6) 7.51 dd (6.8, 2.1) 7.52 dd (6.8, 6.6) 7.29 dd (6.6, 2.1) — 7.27 dd (7.3, 1.6) 7.38 dd (7.3, 7.0) — — 7.53 br.t(7.0) 7.38 dd (7.3, 7.0) 7.27 dd (7.3, 1.6) 5.30 s
7a
4.83 td (5.8, 1.5) 6.18 tdd (17.3, 10.5, 5.8) — 5.43 tdd (17.3, 1.5, 1.5) 5.29 tdd (10.5, 1.5, 1.5) — — — —
8.91 dd (4.2, 1.8) — 7.36 m — 8.07 dd (8.3, 1.8) — 7.37 m — 7.39 m — 7.03 dd (7.3, 1.7)
8
NMR of 8-quinolinol
8.75 dd (4.2, 1.7) 7.35 dd (8.3, 4.2) 8.10 dd (8.3, 1.7) 7.72 dd (8.1, 1.4) 7.46 dd (8.1, 7.6) 7.59 dd (7.6, 1.4) 7.96 dd (8.4, 1.4) 7.43 dd (8.4, 7.6) 7.45 tt (7.6, 1.4) 7.43 dd (8.4, 7.6) 7.69 dd (8.4, 1.4) — — 8.87 dd (4.1, 1.7) 7.57 dd (8.3, 4.1) 8.41 dd (8.3, 1.7) 7.90 dd (8.1, 1.4) 7.61 dd (8.1, 7.4) 7.53 dd (7.4, 1.4) 6.27 qd (15.5, 1.7) 7.17 qd (15.5, 6.9) 1.98 dd (6.9, 1.7) — — — —
8.80 dd (4.2, 1.7) 7.36 dd (8.3, 4.2) 8.10 dd (8.3, 1.7) 7.71 dd (8.1, 1.4) 7.47 dd (8.1, 7.6) 7.59 dd (7.6, 1.4) 7.86 d (8.4) 7.23 dd (8.4, 0.7) — 7.23 dd (8.4, 0.7) 7.86 d (8.4) — —
9.5 : 0.5) that furnished N-benzyl, 8-benzyloxy quinolinium chloride (21, 2.0 g), rods, mp 145–147 °C. Preparation of allyloxy (8), p-nitrobenzyloxy (9), and crotonyloxy (13) derivatives For each experiment, a solution of 8-quinolinol (1, 2.0 g) was dissolved in acetone (15 ml) to which potassium carbonate and the corresponding alkyl halides [allyl bromide (2.0 ml), p-nitrobenzyl chloride (2.3 g) and crotonyl chloride (2.0 ml)] were added and the reaction mixture was refluxed with stirring. Compounds 8, 9, and 10 were formed after 3 h, 2 days, and 5 h, respectively, as revealed by TLC. On usual workup of reaction mixture, the ethyl acetate phase of the respective reaction mixture, yielded pure 8-allyloxy quinoline (8, 1.9 g); 8-p-nitrobenzyloxy quinoline (9, 3.0 g) and 8-crotonyloxy quinoline (13, 2.2 g), irregular plates, mp 98–100 °C. Preparation of acetyloxy (10), benzoyloxy (11), cinnamoyloxy (12), benzene sulfonyloxy (14), and p-toluene sulfonyloxy (15) derivatives
Results and Discussion
Coupling constants are given in parentheses. Solvent (CD3)2SO; 9 H-7′ δ 5.49 s, 15 4′-CH3 δ 2.39 br. s.
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In each experiment, to a solution of 8-quinolinol (1, 2.0 g) in pyridine (2.0 ml) acetic anhydride (2.0 ml), benzoyl chloride (2.0 ml), benzene sulfonyl chloride (2.0 ml), p-toluene sulfonyl chloride (3.0 g), and cinnamoyl chloride (3.0 g) were added and kept at room temperature for 2 h (10), 4 h (11), 10 days (12), and 1 day (14) and (15). On usual workup, organic phase yielded 8-acetoxy quinoline (10, 1.8 g), 8-benzoyloxy quinoline (11, 2.8 g), prismatic rods, mp 120–123 °C; 8-cinnamoyloxy quinoline (12, 3.0 g), irregular transparent plates, mp 63–65 °C; 8-benzene sulfonyloxy quinoline (14, 2.4 g), semicrystalline, mp 176–178 °C, and 8-p-toluene sulfonyloxy quinoline (15, 2.8 g), cylindrical rods, mp 115–117 °C.
a
8.89 dd (4.2, 1.6) 7.58 dd (8.3, 4.2) 8.44 dd (8.3, 1.6) 7.92 dd (7.6, 2.0) 7.65 dd (8.0, 7.6) 7.61 dd (8.0, 2.0) 7.83 dd (7.3, 2.2) 7.47 m 7.47 m 7.47 m 7.83 dd (7.3, 2.2) 7.03d (16.1) 7.91d (16.1) 8.94 dd (4.2, 1.8) 7.42 dd (8.3, 4.2) 8.11 dd (8.3, 1.8) 7.39 dd (8.3, 1.6) 7.35dd (8.3, 7.3) 6.97dd (7.3, 1.6) 7.67 dd (8.5, 0.69) 8.17 d (8.5) — 8.17 d (8.5) 7.67 dd (8.5, 0.69) — — H-2 H-3 H-4 H-5 H-6 H-7 H-2′ H-3′ H-4′ H-5′ H-6′ α CH β CH
8.80 dd (4.2, 1.6) 7.17 dd (8.3, 4.2) 7.91 dd (8.3, 1.6) 7.49 m 7.33 m 7.33 m 2.41 s — — — — — —
9.00 dd (4.5, 1.5) 7.74 dd (8.4, 4.5) 8.75 dd (8.4, 1.5) 8.08 dd (8.1, 1.3) 7.76 dd (8.1, 7.6) 7.48 dd (7.6, 1.3) 8.22 dd (8.3, 1.3) 7.62 dd (8.3, 7.3) 7.77 tt (7.3, 1.3) 7.62 dd (8.3, 7.3) 8.22 dd (8.3, 1.3) — —
8.87 dd (4.2, 1.6) 7.32 dd (8.3, 4.2) 8.08 dd (8.3, 1.6) 7.65 m 7.47 m 7.47 m 7.55 m 7.35 m 7.35 m 7.35 m 7.55 m 6.85d (15.9) 7.59d (15.9)
8.87 dd (4.2, 1.7) 7.31 dd (8.3, 4.2) 8.06 dd (8.3, 1.7) 7.62 m 7.49 m 7.43 m 6.25qd (15.5, 1.7) 7.27 qd (8.5) 1.93 dd (6.9, 1.7) — — — —
14 12a 12 11a 10 9 Proton
1
Table 2. The H NMR chemical shifts and their multiplicities for derivatives 9–15 in CDCl3
13
13a
15
S. Mastoor et al.
NMR study of 8-quinolinol (1) showed six doublet of doublets at δ 8.77 (J2,3 4.2 Hz, J2,4 1.5 Hz, H-2), δ 7.35 (J3,4 8.3 Hz, J3,2 4.2 Hz, H-3), δ 8.08 (J4,3 8.3 Hz, J4,2 1.5 Hz, H-4), δ 7.29 (J5,6 8.2 Hz, J5,7 1.1 Hz, H-5), δ 7.44 (J6,5 8.2 Hz, J6,7 7.5 Hz, H-6), and δ 7.22 (J7,6 7.5 Hz, J7,5 1.1 Hz, H-7). Signal for OH at C-8 was not observed in CDCl3 but in DMSO-d6 appeared at δ 9.76 (Table 1). The proton signals were assigned on the basis of chemical shift arguments and coupling patterns. These assignments were transferred to C-2 to C-7 through HeteroCOSY, whereas that for quaternary carbons was made through 13C NMR and literature.[14] Nucleophilic substitution reaction of 8-quinolinol with different reagents produced several 8-O-substituted derivatives (2–15) and N-alkyl, 8-alkoxy quinolinium halides (16–21). It is worth mentioning that multiplicities in 8-benzyloxy quinoline (7), 8-cinnamoyloxy (12), and 8-crotonyloxy (13) were better resolved in DMSO-d6 (Tables 1–4). Electron withdrawing effect of substituents in compounds 9–15 was more pronouncedly observed in 13C NMR (Table 5) than 1H NMR (Table 2). 8-Acetyloxy quinoline (10) was found to be unstable and promptly hydrolyzed to 8-quinolinol as observed earlier.[15] This is due to the intramolecular neighboring effect of quinoline nitrogen.[15] Among N, O-substituted dialkyl quinolinium halides (16–21), both hydrogen and carbon nuclei showed high frequency chemical shift values as compared with 8-quinolinol (Tables 3 and 6). However, ring A nuclei displayed higher desheilding effects because of the presence of the positive charge on quinoline nitrogen (Tables 3 and 6).
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10.02 dd (5.8, 0.7) 8.09 dd (8.4, 5.8) 8.98 dd (8.4, 0.7) 7.83 m 7.83 m 7.53 dd (6.6, 2.7) 4.12 s — — — — — 5.03 s — — — — —
16
a
16a 9.31 dd (5.8, 1.2) 8.08 dd (8.4, 5.8) 9.17 dd (8.4, 1.2) 7.96 dd (8.1, 1.6) 7.92 dd (8.1, 7.7) 7.76 dd (7.7, 1.6) 4.07 s — — — — — 4.78 s — — — — —
Coupling constants are given in parentheses. Solvent (CD3)2SO; 21 H-7′ δ 5.31 s, H-7″ δ 6.55 s.
H-2 H-3 H-4 H-5 H-6 H-7 H-1′ H-2′ H-3′ H-4′ H-5′ H-6′ H-1″ H-2″ H-3″ H-4″ H-5″ H-6″
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Proton
1
9.93 dd (5.7, 1.2) 8.04 dd (8.4, 5.7) 9.06 dd (8.4, 1.2) 7.85 dd (8.1, 1.1) 7.79 dd (8.1, 7.9) 7.57 br.d (7.9) 4.32 q (7.0) 1.53 t (7.0) — — — — 5.47 q (7.1) 1.65 t (7.1) — — — —
17
Table 3. The H NMR chemical shifts and their multiplicities for derivatives 16–21 in CDCl3
9.57 dd (5.8, 1.4) 8.71 dd (8.4, 5.8) 9.28 dd (8.4, 1.4) 8.02 dd (8.2, 1.4) 7.91 dd (8.2, 8.0) 7.81 dd (8.0, 1.4) 4.27 t (6.6) 1.91 m 0.91 t (7.4) — — — 5.20 t (7.8) 1.96 m 1.04 t (7.4) — — —
18a 10.25 br.d (5.20) 8.15 dd (8.0, 5.2) 9.02 br.d (8.0) 7.81 m 7.81 m 7.54 br.d (7.52) 4.27 t (6.6) 1.94 m 1.45 m 0.94 t (7.4) — — 5.54 t (7.6) 1.94 m 1.53 m 1.00 t (7.4) — —
19a
9.53 dd (5.8, 1.1) 8.13 dd (8.3, 5.8) 9.26 dd (8.3, 1.1) 8.01 dd (7.9, 1.3) 7.92 t (7.9) 7.84 dd (7.9, 1.3) 4.32 t (6.6) 1.92 m 1.46 m 1.33 m 0.86 t (7.1) — 5.23 t (7.7) 1.96 m 1.50 m 1.39 m 0.91 t (7.2) —
20a
9.70 dd (5.8, 1.0) 8.25 dd (8.3, 5.8) 9.38 br.d (8.3) 8.06br.d (8.1) 7.90 dd (8.1, 8.0) 7.78 br.d (8.0) — 6.82 dd (6.5, 1.5) 7.21 m 7.21 m 7.21 m 6.82 dd (6.5, 1.5) — 7.32 m 7.21 m 7.21 m 7.21 m 7.32 m
21
NMR of 8-quinolinol
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13
147.89 121.68 136.10 117.85 127.68 110.23 152.36 138.30 128.55 — — — — — —
1
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13
149.29 121.59 135.77 120.53 126.24 110.02 153.56 140.21 132.40 144.32 127.34 123.65 147.32 123.65 127.34
9 150.47 121.68 136.20 125.97 126.25 121.77 147.38 141.15 129.58 169.83 21.02 — — — —
10
C NMR chemical shifts (δ) for derivatives 9–15 in CDCl3
149.04 121.74 136.41 119.58 126.97 107.85 155.26 139.77 129.45 56.03 — — — — —
2
154.37 139.43 145.88 131.98 127.77 129.34 150.03 142.08 134.52 134.05 135.53 134.19 133.08 134.19 135.53
11a
148.95 121.29 135.82 119.16 126.50 108.34 154.44 138.13 129.28 64.08 14.51 — — — —
3
150.35 121.60 136.08 125.75 126.20 121.60 147.34 141.16 129.51 134.33 128.31 128.87 130.50 128.87 128.87
12
a
Solvent (CD3)2SO; 9 C-7′ δ 69.47, 11* OCO δ 169.99, 12 OCO δ 165.48, αCH δ 117.23, βCH δ 146.83, 15 4′-CH3 δ 21.65.
C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ C-4′ C-5′ C-6′
Carbon
Table 5. The
a
148.14 121.82 136.04 117.71 127.49 111.26 153.32 138.50 128.80 — — — — — —
1a
C NMR chemical shifts (δ) for derivatives 1–4, 6–8 in CDCl3
Solvent (CD3)2SO; 7 C-7′ δ 70.82.
C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ C-4′ C-5′ C-6′
Carbon
Table 4. The
149.04 121.29 135.66 119.16 126.48 108.47 154.70 140.25 129.31 70.22 22.06 10.30 — — —
4
150.41 121.48 135.88 125.68 126.07 121.52 147.29 141.29 129.41 164.83 121.85 147.23 18.08 — —
13
149.31 121.53 135.93 119.37 126.74 108.68 154.97 140.49 129.56 69.03 28.71 28.21 22.53 14.01 —
6
150.79 121.94 135.91 127.16 126.12 122.73 145.49 136.20 129.69 141.58 128.86 128.83 134.03 128.83 128.86
14
148.86 121.70 136.77 119.99 126.94 110.26 153.95 139.65 128.32 130.59 128.62 127.33 127.92 127.33 128.62
7
150.69 121.83 135.80 125.99 126.97 122.46 145.50 133.22 129.63 145 128.75 129.63 141.48 129.63 128.75
15
148.99 121.29 135.4 119.50 126.54 109.13 154.07 140.19 129.24 69.59 132.95 117.95 — — —
8
S. Mastoor et al.
Magn. Reson. Chem. 2014, 52, 115–121
NMR of 8-quinolinol Table 6. The
13
C NMR chemical shifts (δ) for derivatives 16–21 in (CD3)2SO
Carbon C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ C-4′ C-5′ C-6′ C-1″ C-2″ C-3″ C-4″ C-5″ C-6″ a
16a
17a
18
19
20
21
152.40 122.98 147.12 122.55 130.82 115.94 151.63 132.11 130.82 57.42 — — — — — 53.16 — — — — —
151.32 122.93 147.63 122.87 130.90 116.93 149.94 132.44 129.43 66.72 14.46 — — — — 59.69 18.25 — — — —
151.64 122.53 147.76 122.30 130.42 117.28 150.94 132.18 129.09 72.18 21.84 10.29 — — — 64.07 25.21 10.67 — — —
152.56 122.87 147.20 122.87 130.45 116.42 150.23 132.41 129.30 70.68 30.83 19.37 13.63 — — 63.53 34.77 19.37 13.68 — —
151.52 122.27 147.67 122.49 130.34 117.16 149.78 132.13 129.08 70.57 28.09 27.73 21.82 13.76 — 62.76 31.67 27.80 21.86 13.76 —
152.96 123.39 149.27 123.08 131.18 118.31 149.60 136.51 130.10 132.90 126.12 128.84 129.49 128.84 126.12 136.51 128.84 129.23 129.49 129.23 128.84
Solvent CDCl3; 21 C-7′ δ 72.12, C-7″ δ 65.73.
Acknowledgement The authors thankfully acknowledge the help and cooperation of Dr Muhammad Ali Versani, Associate Professor at Federal Urdu University, Karachi, Pakistan, for explaining the instrumental details.
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