Analyzing 13C-NMR spectra of several polysubstituted quinolines

JOURNAL OF SCIENCE OF HNUE Chemical and Biological Sci., 2012, Vol. 57, No. 8, pp. 3-8 This paper is available online at ANALYZING 13C-NMR SPECTRA OF SEVERAL POLYSUBSTITUTED QUINOLINES Nguyen Huu Dinh1, Le Van Co2 and Hoang Thi Tuyet Lan3 1Faculty of Chemistry, Hanoi National University of Education 2Faculty of Chemistry, Tay Nguyen University 3University of Transportation, Hanoi Abstract. The NMR spectra of 15 novel quinolines containing 11 - 34 carbon atoms and bearing substituents such as hydroxyl, sunfo, chloro, bromo, amino, azo and carboxymetoxy groups were recorded in DMSO at 298 - 300 K. For seven quinolines, the 13C-NMR signals were assigned on the basis of an analyzation of the cross peaks in the HSQC and HMBC spectra. For the others, the assignation of 13C-NMR signals was accomplished using chemical shifts of analogous compounds. The received data well agree with the predicted structure of the examined quinolines. Keywords: Quinolines skeleton, 13C-NMR spectra, HSQC, HMBC. 1. Introduction The quinoline skeleton has been used as the basis for the design of many synthetic antimalarial [1], antibacterial, antifungal [2, 3], anti-tuberculosis [4, 5] and anticancer [6] compounds. Almost all these compound are polysubstituted quinolines which have been synthesized from industrial petrochemical products. Some time ago we had focused our attention on several main components of vegetable essential oils that, owing to their structure, could act as a good substrate in the preparation of heterocyclic compounds. For example, some furoxans were prepared from safrole (in sassafras oil) [7] and thiazolidinones and indoles were synthesized from anethole (in star anise oil) [8]. Recently [9] we found a new method of quinoline cyclization using eugenol, the main constituent of Ocimum sanctum L. oil (a cheap natural source for the commercial extraction of eugenol). This method allows synthesis of a series of novel polysubstituted quinolines. Herein we report the results of 13C-NMR spectra of several novel polysubstituted quinolines for structure determination. Received May 14, 2012. Accepted July 23, 2012. Chemistry Subject Classification: 10401. Contact Nguyen Huu Dinh, e-mail address: nguyenhuusp@yahoo.com 3 Nguyen Huu Dinh, Le Van Co and Hoang Thi Tuyet Lan 2. Content 2.1. Experiment The analyzed compounds (Q1-Q15) were synthesized from (6-hydroxy-3-sulfoquinolin-7-yloxy) acetic acid (Q) using traditional methods [9,10]. Their predicted structure and recorded spectra are presented in Table 1. Table 1. The predicted structure of examined quinolines Q1 - Q15 R1 R2 R3 Spectra R1 R2 R3 Spectra Q H H OH 1H, 13C, HSQC, HMBC Q8 NO2 H OH 1H, 13C, HSQC, HMBC Q1 H H OCH3 1H, 13C Q9 NH2 H OH 1H, 13C, HMBC Q2 H H NHNH2 1H, 13C Q10 N=N-C6H5 H OH 1H, 13C, HMBC Q3 Cl H OH 1H, 13C, HMBC Q11 N=N-C6H4Me-p H OH 1H, 13C Q4 Br H OH 1H, 13C, HMBC Q12 N=N-C6H4NO2-p H OH 1H, 13C Q5 Br H OMe 1H, 13C Q13 N=N-C6H4SO3Na-p H OH 1H, 13C Q6 Br H NHNH2 1H, 13C Q14 N=N-C6H4-p (∗) H OH 1H, 13C Q7 H MeCO OH 1H, 13C, HMBC Q15 N=N-C6H3(OMe,Fu) H OH 1H, 13C (*) see Figure 3 The 1H-NMR, 13C-NMR, HSQC and HMBC spectra were recorded on a Bruker AVANCE 500 MHz, in d6-DMSO, with TMS as the internal standard, at 298 - 300 K. 2.2. Results and discussion All of the resonance signals in the 1H-NMR spectra of Q, Q1 - Q15 were assigned on the basis of an analyzation of the spin-spin splitting patterns [9, 10]. The examined compounds contain 11 - 16 unequivalent carbon atoms. In order to assign these carbon atoms, in most cases the use of a 2D-NMR spectra was necessary but in some cases it was not needed. In Q1 and Q2 group R3 is far from the quinoline ring so the ordering of chemical 4 Analyzing 13C-NMR spectra of several polysubstituted quinolines shifts for C2 - C10 of Q1, Q2 is similar to that of Q (Table 2). Because eleven 13C-NMR signals of Q were accurately assigned on the basis of an analyzation of the cross peaks in the HSQC and HMBC spectra [9], the determination of the carbon signals of Q1 and Q2 was carried out without use of a 2D-NMR spectra. In Q3, Q4, Q8, Q9 and Q10, group R1 is attached to the quinoline ring so it strongly changes the chemical shifts of C2 - C10, therefore for their determination the 2D-NMR spectra were recorded and analyzed. For instance, the carbon signals of Q8 were assigned as below. Figure 1. HSQC spectrum of Q8 The cross peaks in the HSQC spectrum of Q8 (Figure 1) show the signals of C2, C4, C8 and C11. Figure 2. Partial HMBC spectrum of Q8 5 Nguyen Huu Dinh, Le Van Co and Hoang Thi Tuyet Lan In the HMBC spectrum of Q8 (Figure 2), the signals of C2, C4, C8 have been known from the HSQC spectrum. Cross peak c belongs to H2 and C4, while cross peaks a and b show that two signals at 141.26 and 138.25 ppm associate with C3 and C9. The signal at 138.25 ppm has cross peaks e and i with H4 and H8 so this signal belongs to C9, therefore the signal at 141.26 ppm was assigned to C3. Cross peak f of H4 shows the signal of C5. The two cross peaks g andm show the signal of C7. Cross peaks h and j show the signals of C6 and C10 respectively. The signals of C11 and C12 can be recognized according to their chemical shifts without 2D-NMR spectra. Similarly, all carbon signals of Q3, Q4, Q8, Q9 and Q10 were assigned on the basis of analyzing their HMBC spectra. The difference between Q5, Q6 and Q4 is in group R3 while the difference between Q11, Q12, Q13 and Q10 is in structure of the substitutent group (R4) in the para position of phenyl moiety. Since R3 and R4 are removed from the quinoline ring (Q-O-CH2-CO-R 3 and Q-N=N-C6H4-R 4-p), they very weekly influence the chemical shifts of C2 - C10. This allows the determination of the quinoline carbon signals of Q5, Q6, Q11, Q12, Q13 without their HMBC spectra using the carbon signals of Q4 and Q10 as indicators. For ester Q5, the determination of carbon signals was also made using its HMBC spectrum, receiving the same data as when not using the HMBC spectrum. Table 2. The resonance signals of C2-C12 in the examined compounds, δ, ppm C2 C3 C4 C5 C6 C7 C8 C9 C10 C11 C12 Other Q 144.94 138.37 132.37 110.70 148.77 152.16 108.47 143.70 124.00 66.30 171.42 - Q1 140.07 138.82 134.66 110.14 150.16 154.29 101.52 138.49 125.14 65.57 168.16 Me: 52.21 Q2 145.26 143.35 130.10 110.06 147.26 149.88 108.89 139.27 123.12 67.08 166.10 - Q3 141.25 140.45 133.16 122.37 146.40 153.45 101.96 136.45 113.66 66.03 169.05 - Q4 141.77 140.70 134.75 123.35 147.31 152.63 103.18 137.72 104.93 65.92 168.70 - Q5 142.55 140.65 133.75 123.20 146.95 152.03 104.28 138.67 105.02 65.82 168.27 Me: 52.23 Q6 142.60 140.13 128.98 122.56 144.95 150.35 104.20 140.12 108.52 67.41 165.97 - Q7 143.87 139.18 140.29 122.00 142.08 154.57 103.90 139.65 123.27 65.79 168.74 MeCO: 20.33; 168.41 Q8 143.08 141.26 138.33 115.77 144.70 151.38 108.90 132.85 127.05 66.00 169.15 - Q9 144.79 137.28 126.16 131.22 135.65 153.41 106.98 142.33 114.12 74.66 173.13 - Q10 144.39 141.18 126.53 128.10 166.98 153.07 113.40 143.17 123.95 65.23 169.20 - Q11 145.76 141.12 126.38 128.15 167.45 152.32 115.42 142.67 123.57 65.35 169.34 Me: 19.28 Q12 145.79 141.56 129.53 126.42 169.10 152.70 115.54 144.37 123.92 65.10 172.86 - Q13 145.89 141.01 125.36 128.18 168.15 152.40 115.43 144.64 123.51 65.16 169.38 - Q14 145.82 141.21 128.07 128.17 167.33 152.32 115.22 142.55 123.46 65.26 169.37 - Q15 145.96 141.42 126.56 128.97 169.22 152.58 115.60 144.76 123.50 65.03 171.15 - 6 Analyzing 13C-NMR spectra of several polysubstituted quinolines For ester Q7, the determination of carbon signals was made using its HMBC spectrum. In the HMBC spectrum there is no cross peak between the H2 and carbonyl carbon of the acetyl group. This indicates that the acetyl group is not attached to a quinoline N atom. The chemical shifts of C2 - C12 of Q14 and Q15 are similar to those of Q11. The resulting assignations of C2 - C12 in the examined compounds are listed in Table 2. In the substituted phenyl moiety of compounds Q11, Q12 and Q13 there are 4 aromatic unequivalent carbon atoms: Ci, Co, Cm and Cp. Their signals can be recognized according to their chemical shifts as well as by using data of Q11 and of same substituted phenyl moiety of analogous azo compounds from [11] as indicators. The structure of Q14 and Q15 is presented in Figure 3. The Q14 molecule has 34 carbon atoms. However, in its 13C-NMR spectrum there are only 15 carbon signals. This shows that two moieties of Q14 (Q-N=N-C6H4-p)2 are equivalent. Figure 3. Structure of Q14 and Q15 Chemical shifts of C2 - C12 and Ci, Co and Cm of Q14 are similar to those of Q11 while the chemical shift of Cp is much larger than that of Q11 (Table 3). No doubt the deshielding anisotropic effect of neighbouring benzene rings moves Cp downfield. The carbon signals in second moiety of Q15 were assigned using carbon signals of the same moiety of analogous azo compounds in [12]. Table 3. The carbon signals in the second moiety of Q10-Q15, δ, ppm Ci Co Co’ Cm Cm’ Cp Others Q10 142.84 118.35 118.35 130.03 130.03 127.65 - Q11 147.10 122.97 122.97 129.37 129.37 144.64 Me: 21.13 Q12 147.08 117.41 117.41 125.76 125.76 145.38 - Q13 147.10 117.43 117.43 129.37 129.37 144.64 - Q14 144.43 118.86 118.86 138.08 138.08 162.32 - Q15 131.22 156.51 114.13 113.09 119.97 125.38 Cq: 150.61; Cr: 112.99; Cs: 9.21; MeO: 56.03 7 Nguyen Huu Dinh, Le Van Co and Hoang Thi Tuyet Lan 3. Conclusion The NMR spectra of 15 novel quinolines containing 11 - 34 carbon atoms bearing various substituents such as hydroxyl, sunfo, chloro, bromo, amino, azo and cacboxymetoxy groups (Q1 - Q15) were recorded in DMSO at 298 - 300 K. For seven quinolines (Q, Q3, Q4, Q7, Q8, Q9 and Q10), the 13C-NMR signals were assigned on the basis of analyzing cross peaks in the HSQC and HMBC spectra. For the others, the assignation of 13C-NMR signals was accomplished using chemical shifts of analogous compounds. The received data well agree with the predicted structure of the examined quinolines. Acknowledgements. This work was supported by the National Foundation for Science and Technology Development (NAFOSTED) of Vietnam. REFERENCES [1] S. Meshnick and M. Dobson, 2001. Antimalarial Chemotherapy. Mechanisms of Action, Resistance, and New Directions in Drug Discovery. Humana Press. [2] A. Mohammed, N. Abdel-Hamid, F. Maher and A. Farghaly, 1992. Coll. Czech. Chem. Commun., 57, 1547. [3] L. 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