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Journal of the Chilean Chemical Society

versão On-line ISSN 0717-9707

J. Chil. Chem. Soc. vol.60 no.1 Concepción mar. 2015

http://dx.doi.org/10.4067/S0717-97072015000100008 

 

STUDIES ON THE ALKYLATION OF QUINOLIN-2(1H)-ONE DERIVATIVES

 

CHIA-LING CHEN1, I-LI CHEN2, JIH-JUNG CHEN2, DAU-CHANG WEI2, HAN-JIE HSIEH2, KEN-MING CHANG3, CHERNG-CHYI TZENG3 AND TAI-CHI WANG2*

1Department of Pharmacy, KUO General Hospital, Tainan City 700, Taiwan
2
Department of Pharmacy, Tajen University, Pingtung 907, Taiwan
3
Departament of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan


ABSTRACT

Alkylation of quinolin-2(1H)-one (1) and its C(6) and C(7) substituted dervatives (OMe, OBn, and Cl) with 2-bromoacetophenone or chloroacetone under basic condition (K2CO3 in DMF) gave a mixture of N1- and O2- alkylated products with the former one as a major product. However, alkylation of 8-methoxy-, 8-benzyloxy-, and 8-chloro- quinolin-2(1H)-ones under the same reaction conditions gave exclusively O2-alkylated products.

Keywords: N-Alkylation; O-Alkylation; Quinolin-2(1H)-one.


 

INTRODUCTION

Quinolin-2(1H)-one (carbostyril) skeleton is present in a large number of biologically active compounds which exhibit antiplatelet, anti-inflammatory, anti-ulcer, vasodilatory, and phosphodiesterase inhibitory activities1-12. Carteolol, for example, has been used clinically as a ß-adrenergic blocking agent8. Over the past few years, we were particularly interested in the synthesis of α-methylene-γ-butyrolactones bearing heterocycles such as coumarins, flavones, xanthones, quinolines, and quinolin-2(1H)-ones and the evaluation of their cardiovascular and cytotoxic activities9-14. Among these heterocycles, coumarins exhibited the most potent inhibitory activities on the high-K+-medium, Ca2+-induced vasoconstriction, and the norepinephrine-induced phasic and tonic vasoconstrictions, while quinolin-2(1H)-ones proved to be the most active against platelet aggregation. A number of quinolin-2(1H)-one α-methylene-γ-butyrolactones were found to exhibit potent antiproliferative activities14.

These biologically active quinolin-2(1H)-one derivatives were synthesized from their hydroxyl precursors by alkylation and the Reformatsky-type condensation. The Reformatsky-type condensation is quite straightforward while the alkylation of quinolin-2(1H)-one involves a competitive alkylation leading to the mixture of N1- and O2- alkylated products. Although it is well known that alkylation of 2-pyridones gave a mixture ofboth N- and O- alkylated products,15-17 relatively few systematic studies of this phenomenon have been published. Hopkins et al18 demonstrated that alkylation of 2-pyridone with benzyl chloride and sodium salt in DMF occurred at N1-position whereas using the silver salt in benzene afforded exclusively the O2-alkylated product. The Mitsunobu reaction has also been applied to alkylate 2-pyridones to discover the relationship between the ratio of N- and O- alkylation products.19,20

The alkylation of C-5 substituted 2-phenyl-4-quinolones was also investigated and showed that the ratio of N-alkylation versus O-alkylation is highly dependent on the property of C-5 group. Both N-alkylation and O-alkylation products were detected for C-5 methoxy derivative while the sole product of N-alkylation was obtained for the C-5 hydroxy derivative. The alkylation of these 2-phenyl-4-quinolones was conducted under several conditions (NaH/THF, NaH/DMF, K2CO3/acetone, K2CO3/DMF) at different temperatures. The K2CO3/DMF system and temperature elevation led to the highest yields but there was no significant influence on the regioselectivity compared to the other systems used.21 Studies on N-alkylation versus O-alkylation in various ambident heterocyclic compounds under phase transfer conditions have also been reported.22-25 We have obtained a mixture of N1- and O2- alkylated products from the alkylation of quinolin-2(1H)-one (1) with N1-alkylation as the major product (Scheme 1)10. Alkylation of 6-acetoxyquinolin-2(1H)-one (2) gave a mixture of N1- and O2- alkylated products with N1-alkylation as the major product11. However, a sole O2-alkylated product was obtained from the alkylation of 8-acetoxyquinolin-2(1H)-one (9) with 2-bromoacetophenone and potassium carbonate in DMF12. Guo et. al. have also reported that the alkylation of 8-hydroxyquinolin-2(1H)-one with 3-methoxybenzyl bromide under basic condition to afford a mixture of N1- and O2- alkylated products with the former one as a major product26. Alkylation of 8-hydroxyquinolin-2(1H)-one was similar to 2 but was distincted from 9 prompted us to explore the alkylation of various quinolin-2(1H)-one derivatives. The steric and electronic effects of different substituents which influence the N1- and O2- alkylation of quinolin-2(1H)-ones are described.

 

Scheme 1. Alkylation of quinolin-2(1H)-one with 2-bromoacetophenone.

 

RESULTS AND DISCUSSION

Alkylation of quinolin-2(1H)-one (1) with 2-bromoacetophenone and potassium carbonate in DMF gave a mixture of N1- and O2- alkylated products (13a and 13b respectively) with 13a as a major product (Scheme 1) but not a sole product as our previous report10. The structure of 13a was confirmed by the long-range 1H,13C-HETCOR experiment in which N(1)-CH2 (5.81 ppm) was coupled to C-atoms with resonances of 192.37 (2J), 162.11 (3J), 139.55 (3J), and 48.68 (1J) ppm corresponding to C(2'), C(2), C(8a), and C(1') respectively. Structure of 13b was also confirmed by 1H,13C-HETCOR experiment in which O(2)-CH2 (5.76 ppm) was coupled to C-atoms with resonances of 194.49 (2J), 160.68 (3J), and 67.48 (1J) ppm corresponding to C(2'), C(2), and C(1') respectively. It is worth to mention that one-dimensional 1H-NMR spectra along is not enough to assign the site of alkylation since chemical shifts of N(1)-CH2 (5.81 ppm) and O(2)-CH2 (5.76 ppm) are not distinguishable. However, one-dimensional 13C-NMR spectra provide very useful informations in which C(1') showed a upfield shift at 48.68 ppm for N1-alkylated product 13a and a downfield shift at 67.48 ppm for O2-alkylated product 13b. A view of a single molecule of 13a and 13b respectively are given in Figure 1.

 

Figure 1. X-Ray crystallographic structures of 13a and 13b

 

Under the same alkylating conditions, quinolin-2(1H)-one substituted with an electron-donating group such as methoxy 3, benzyloxy 4, or with an electron-withdrawing group such as chloro 5, at C(6)-position gave a mixture of N1- and O2- alkylated products with the N1-alkylation as the major product as shown in Scheme 1. Therefore, the electronic environment did not affect the type of alkylation. Accordingly, alkylation of C(7)-substituted quinolin-2(1H)-ones 6, 7, and 8 afforded N1-alkylated products 18a, 19a, and 20a as major products.

However, this type of alkylation can not be applied to C(8)-substituted quinolin-2(1H)-ones. Treatment of 8-methoxyquinolin-2(1H)-one (10) with 2-bromoacetophenone and potassium carbonate in DMF gave O2-alkylated product, 8-methoxy-2-(2-oxo-2-phenylethoxy) quinoline (22b), as a sole product in a 75% yield. Accordingly, O2-alkylated products 21b12, 23b, and 24b were obtained from the alkylation of their respective precursors 9, 11, and 12.

To confirm the application of this type of alkylation, further experiments were carried out by using chloroacetone as an alkylating agent as shown in Scheme 2. Treatment of C(6) and C(7) substituted quinolin-2(1H)-ones with chloroacetone and potassium carbonate in DMF gave a mixture of N1- and O2-alkylated products with the former one as a major product. The typical peak of 1H-NMR spectra are not distinguishable, for example, N(1)-CH2 (5.11 ppm) for 25a and O(2)-CH2 (5.04 ppm) for 25b. However, 13C-NMR spectra provide very useful informations in which C(1') showed a downfield shift at 70.07 ppm for O2-alkylated product 25b and a upfield shift at 52.03 ppm for N1-alkylated product 25a. Alkylation of C(8)-substituted quinolin-2(1H)-ones under the same reaction conditions afforded O2-alkylated product as a sole product. Therefore, the site of alkylation could be controlled mostly by the steric effect in which less hindered C(6) and C(7) substituted quinolin-2(1H)-ones alkylated at N1- and O2- positions with the former one as a major product while C(8) substituted counterparts alkylated exclusively at less hindered O2-position.

 

Scheme 2. Alkylation of quinolin-2(1H)-one with chloroacetone.

 

Alkylating agents may also affect the regioselectivity in which the N/O ratio for higher bulky 2-bromoacetophenone is less than that of less bulky chloroacetone due to higher steric hindrance of N-alkylation than that of O-alkylation. For example, the N/O ratio is 2.7 (62/23) for 6-benzyloxy derivative (entry 4, Scheme 1) using 2-bromoacetophenone as an alkylating agent while the N/O ratio is 7.1 (71/10) using chloroacetone (entry 4, Scheme 2) as an alkylating agent.

CONCLUSIONS

In conclusion, we report herein the selective alkylation of certain substituted quinolin-2(1H)-one derivatives. Our results indicated that alkylation of relatively bulky 8-methoxy-, 8-benzyloxy-, and 8-chloro- quinolin-2(1H)-ones under classical conditions (2-bromoacetophenone or chloroacetone, DMF, K2CO3) gave exclusively O2-alkylated products. This selectivity can not be applied to C(6) and C(7) substituted quinolin-2(1H)-one counterparts in which alkylation occurred at both N1- and O2- positions with the former one as a major product. Therefore, alkylation of substituted quinolin-2(1H)-ones was controlled by the steric effect but not the electronic effect.

EXPERIMENTAL

TLC: Precoated (0.2 mm) silica gel 60-F254 plates from EM Laboratories, Inc.; detection by UV light (254 nm). M.p.: Electrothermal IA9100 digital melting-point apparatus; uncorrected. 1H and 13C-NMR spectra: Varian-Unity-400 spectrometer at 400 and 100 MHz or Varian-Gemini-200 spectrometer at 200 and 50 MHz, chemical shifts d in ppm with SiMe4 as an internal standard (= 0 ppm), coupling constants J in Hz. Elemental analyses were carried out on a Heraeus CHN-O-Rapid elemental analyzer, and results were within ± 0.4% of calculated values.

1-(2-Oxo-2-phenylethyl)quinomi-2(1H)-one (13a) and 2-(2-Oxo-2-phenylethoxy)quinoline (13b)

Quinolin-2(1H)-one (1.45 g, 10 mmol), K2CO3 (1.38 g, 10 mmol), and dry DMF (50 mL) were stirred at rt for 30 min. To this solution was added 2-bromoacetophenone (1.99 g, 10 mmol) in dry DMF (10 mL) in one portion. The resulting mixture was continued to stir at rt for 24 h (TLC monitoring), and then poured into ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×75 mL). The organic layer was combined, washed with H2O, dried (Na2SO4), and then evaporated to give a brown solid which was purified by column chromatography on silica gel (AcOEt/Hexane 1:1). The proper fractions were combined and evaporated to furnish a residual solid which was crystallized from CH2Cl2 /Et2O 1:10 to afford 13a (1.74 g, 66 %) and 13b (0.17 g, 7 %).

13a: Mp 164-165 oC. 1H NMR (400 MHz, CDCl3): δ 5.81 (s, 2H, H-C(1')), 6.75 (d, 1H, J = 9.6 Hz, H-C(3)), 6.98 (d, 1H, J = 9.6 Hz, ArH), 7.19-7.22 (m, 1H, ArH), 7.42-7.67 (m, 5H, ArH), 7.75 (d, 1H, J = 9.6 Hz, H-C(4)), 8.08-8.10 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3): δ 48.68 (C(1')), 114.02, 120.78, 121.17, 122.26, 128.10, 128.89, 129.02, 130.68, 133.95, 134.87, 139.55, 139.86, 162.11 (C(2)), 192.37 (C(2')). Anal. Calcd for C17H13NO2: C, 77.55; H, 4.98; N, 5.32. Found: C, 77.52; H, 5.01; N, 5.35.

13b: Mp 115-116 oC. 1H NMR (200 MHz, CDCl3): δ 5.76 (s, 2H, H-C(1')), 7.10 (d, 1H, J = 8.8 Hz, H-C(3)), 7.32-7.73 (m, 7H, ArH), 8.01-8.08 (m, 3H, ArH). 13C NMR (50 MHz, CDCl3): δ 67.48 (C(1')), 112.75, 124.28, 125.42, 127.24, 127.40, 127.94, 128.75, 129.49, 133.49, 135.08, 139.23, 146.02, 160.68 (C(2)), 194.49 (C(2')). Anal. Calcd for C17H13NO2: C, 77.55; H, 4.98; N, 5.32. Found: C, 77.40; H, 5.00; N, 5.31.

6-Memoxy-1-(2-oxo-2-phenylemyl)quinomi-2(1H)-one (15a) and 6-Methoxy-2-(2-oxo-2-phenylethoxy)quinoline (15b)

Prepared from 6-methoxyquinolin-2(1H)-one and 2-bromoacetophenone by the same procedure as described for 13a and 13b. 15a: 80 % yield. Mp 196-197 oC. 1H NMR (400 MHz, CDCl3): δ 3.83 (s, 3H, MeO), 5.79 (s, 2H, H-C(1')), 6.77 (d, 1H, J = 9.6 Hz, H-C(3)), 6.92 (d, 1H, J = 9.2 Hz, H-C(8)), 7.02 (d, 1H, J = 2.8 Hz, H-C(5)), 7.06 (dd, 1H, J = 9.2, 2.8 Hz, H-C(7)), 7.51-7.54 (m, 2H, ArH), 7.62-7.66 (m, 1H, ArH), 7.69 (d, 1H, J = 9.2 Hz, H-C(4)), 8.06-8.09 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3): δ 48.84 (C(1¢)), 55.65 (MeO), 110.77, 115.36, 119.33, 121.50, 121.62, 128.10, 128.89, 133.96, 134.00, 134.84, 139.39, 154.79, 161.72 (C(2)), 192.54 (C(2¢)). Anal. Calcd for C18H15NO3: C, 73.71; H, 5.15; N, 4.78. Found: C, 73.65; H, 5.15; N, 4.68.

15b: 7 % yield. Mp 94-95 oC. 1H NMR (400 MHz, CDCl3): δ 3.88 (s, 3H, MeO), 5.74 (s, 2H, H-C(1¢)), 7.04 (d, 1H, J = 2.4 Hz, H-C(5)), 7.08 (d, 1H, J = 8.8 Hz, H-C(3)), 7.23 (dd, 1H, J = 8.8, 2.4 Hz, H-C(7)), 7.50-7.54 (m, 2H, ArH), 7.60-7.62 (m, 1H, ArH), 7.63 (d, 1H, J = 8.8 Hz, H-C(8)), 7.95 (d, 1H, J = 8.8 Hz, H-C(4)), 8.05-8.07 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3): δ 55.75 (MeO), 67.74 (C(1¢)), 106.33, 113.10, 121.46, 126.23, 128.19, 128.70, 129.01, 133.76, 135.32, 138.57, 141.55, 156.52, 159.63 (C(2)), 194.95 (C(2¢)). Anal. Calcd for C18H15NO3: C, 73.71; H, 5.15; N, 4.78. Found: C, 73.78; H, 5.29; N, 4.60.

6-Benzyloxy-1-(2-oxo-2-phenylethyl)quinolin-2(1H)-one (16a) and 6-Benzyloxy-2-(2-oxo-2-phenylethoxy)quinoline (16b)

Prepared from 6-benzyloxyquinolin-2(1H)-one and 2-bromoacetophenone by the same procedure as described for 13a and 13b. 16a: 62 % yield. Mp 177-178 oC. 1H NMR (400 MHz, CDCl3): δ 5.09 (s, 2H, CH2O), 5.78 (s, 2H, H-C(1¢)), 6.76 (d, 1H, J = 9.2 Hz, H-C(3)), 6.91 (d, 1H, J = 9.2 Hz, H-C(8)), 7.10 (d, 1H, J = 2.8 Hz, H-C(5)), 7.13 (dd, 1H, J = 8.8, 2.8 Hz, H-C(7)), 7.31-7.44 (m, 5H, ArH), 7.51-7.55 (m, 2H, ArH), 7.63-7.68 (m, 2H, ArH), 8.07-8.09 (m, 1H, ArH), 8.08 (d, 1H, J = 9.2 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 48.87 (C(1¢)), 70.55 (CH2O), 112.19, 115.37, 119.98, 121.49, 121.77, 127.42, 128.15, 128.66, 128.92, 133.99, 134.23, 134.84, 136.52, 139.39, 153.91, 161.77 (C(2)), 192.55 (C(2¢)). Anal. Calcd for C24H19NO3: C, 78.03; H, 5.18; N, 3.79. Found: C, 77.68; H, 5.21; N, 3.66.

16b: 23 % yield. Mp 145-146 oC. 1H NMR (400 MHz, CDCl3): δ 5.14 (s, 2H, CH2O), 5.75 (s, 2H, H-C(1¢)), 7.09 (d, 1H, J = 8.8 Hz, H-C(3)), 7.13 (d, 1H, J = 2.8 Hz, H-C(5)), 7.32 (dd, 1H, J = 9.2, 2.8 Hz, H-C(7)), 7.34-7.37 (m, 1H, ArH), 7.38-7.43 (m, 2H, ArH), 7.46-7.49 (m, 2H, ArH), 7.51-7.54 (m, 2H, ArH), 7.61-7.63 (m, 1H, ArH), 7.64 (d, 1H, J = 9.2 Hz, H-C(8)), 7.95 (d, 1H, J = 8.8 Hz, H-C(4)), 8.05-8.08 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3): δ 67.83 (C(1¢)), 70.54 (CH2O), 107.82, 113.16, 121.91, 126.20, 127.78, 128.20, 128.32, 128.74, 128.88, 129.02, 133.77, 135.31, 136.95, 138.66, 141.61, 155.68, 159.71 (C(2)), 194.89 (C(2¢)). Anal. Calcd for C24H19NO3: C, 78.03; H, 5.18; N, 3.79. Found: C, 78.00; H, 5.20; N, 3.78.

6-Chloro-1-(2-oxo-2-phenylethyl)quinolin-2(1H)-one (17a) and 6-Chloro-2-(2-oxo-2-phenylethoxy)quinoline (17b)

Prepared from 6-chloroquinolin-2(1H)-one and 2-bromoacetophenone by the same procedure as described for 13a and 13b. 17a: 64 % yield. Mp 213214 oC. 1H NMR (200 MHz, CDCl3): δ 5.78 (s, 2H, H-C(1¢)), 6.78 (d, 1H, J = 9.5 Hz, H-C(3)), 6.91 (d, 1H, J = 9.0 Hz, H-C(8)), 7.38 (dd, 1H, J = 9.0, 2.4 Hz, H-C(7)), 7.50-7.57 (m, 2H, ArH), 7.56 (d, 1H, J = 2.4 Hz, H-C(5)), 7.63-7.67 (m, 1H, ArH), 7.87 (d, 1H, J = 9.5 Hz, H-C(4)), 8.05-8.10 (m, 2H, ArH). 13C NMR (50 MHz, CDCl3): δ 48.82 (C(1¢)), 115.57, 121,79, 122.54, 127.78, 128.09, 128.16, 129.00, 130.65, 134.19, 134.69, 138.16, 138.72, 161.86 (C(2)), 192.07 (C(2¢)). Anal. Calcd for C17H12NO2Cl: C, 68.58; H, 4.06; N, 4.70. Found: C, 68.47; H, 4.07; N, 4.77.

17b: 28 % yield. Mp 123-124 oC. 1H NMR (400 MHz, CDCl3): δ 5.76 (s, 2H, H-C(1¢)), 7.13 (d, 1H, J = 8.8 Hz, H-C(3)), 7.49 (dd, 1H, J = 8.8, 2.4 Hz, H-C(7)), 7.51-7.55 (m, 2H, ArH), 7.61-7.66 (m, 2H, ArH), 7.69 (d, 1H, J = 2.4 Hz, H-C(5)), 7.96 (d, 1H, J = 8.8 Hz, H-C(8)), 8.05 (d, 1H, J = 8.8 Hz, H-C(4)), 8.04-8.06 (m, 1H, ArH). 13C NMR (100 MHz, CDCl3): δ 67.80 (C(1¢)), 114.06, 126.27, 126.54, 128.16, 129.01, 129.07, 129.94, 130.42, 133.89, 135.15, 138.56, 144.69, 160.14 (C(2)), 194.45 (C(2¢)). Anal. Calcd for C17H12NO2Cl: C, 68.58; H, 4.06; N, 4.70. Found: C, 68.45; H, 4.08; N, 4.73.

7-Methoxy-1-(2-oxo-2-phenylethyl)quinolin-2(1H)-one (18a) and 7-Methoxy-2-(2-oxo-2-phenylethoxy)quinoline (18b)

Prepared from 7-methoxyquinolin-2(1H)-one and 2-bromoacetophenone by the same procedure as described for 13a and 13b. 18a: 65 % yield. Mp 171-172 oC. 1H NMR (400 MHz, CDCl3): δ 3.78 (s, 3H, MeO), 5.76 (s, 2H, H-C(1¢)), 6.44 (d, 1H, J = 2.4 Hz, H-C(8)), 6.60 (d, 1H, J = 9.2 Hz, H-C(3)), 6.80 (dd, 1H, J = 8.8, 2.4 Hz, H-C(6)), 7.49 (d, 1H, J = 8.8 Hz, H-C(5)), 7.51-7.55 (m, 2H, ArH), 7.63-7.65 (m, 1H, ArH), 7.68 (d, 1H, J = 9.6 Hz, H-C(4)), 8.07-8.10 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3): δ 49.14 (C(1¢)), 55.74 (MeO), 99.42, 109.60, 115.34, 118.24, 128.38, 129.18, 130.69, 134.25, 135.14, 139.98, 141.45, 162.08, 162.77 (C(2)), 192.95 (C(2¢)). Anal. Calcd for C18H15NO3: C, 73.71; H, 5.15; N, 4.78. Found: C, 73.70; H, 5.17; N, 4.78.

18b: 12 % yield. Mp 137-138 oC. 1H NMR (400 MHz, CDCl3): δ 3.87 (s, 3H, MeO), 5.77 (s, 2H, H-C(1¢)), 6.96 (d, 1H, J = 8.8 Hz, H-C(3)), 7.01 (dd, 1H, J = 8.8, 2.4 Hz, H-C(6)), 7.07 (d, 1H, J = 2.4 Hz, H-C(8)), 7.50-7.55 (m, 2H, ArH), 7.59 (d, 1H, J = 9.2 Hz, H-C(5)), 7.61-7.65 (m, 1H, ArH), 7.96 (d, 1H, J = 8.8 Hz, H-C(4)), 8.06-8.09 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3): δ 55.64 (MeO), 67.78 (C(1¢)), 106.76, 110.24, 116.69, 120.47, 128.22, 128.66, 129.00, 133.77, 135.27, 139.16, 148.05, 161.20, 161.51 (C(2)), 194.75(C(2¢)). Anal. Calcd for C18H15NO3: C, 73.71; H, 5.15; N, 4.78. Found: C, 73.47; H, 5.24; N, 4.39.

7-Benzyloxy-1-(2-oxo-2-phenylethyl)quinolin-2(1H)-one (19a) and 7-Benzyloxy-2-(2-oxo-2-phenylethoxy)quinoline (19b)

Prepared from 7-benzyloxyquinolin-2(1H)-one and 2-bromoacetophenone by the same procedure as described for 13a and 13b. 19a: 79 % yield. Mp 185-186 oC. 1H NMR (400 MHz, CDCl3): δ 4.99 (s, 2H, CH2O), 5.66 (s, 2H, H-C(1¢)), 6.45 (d, 1H, J = 2.4 Hz, H-C(8)), 6.57 (d, 1H, J = 9.6 Hz, H-C(3)), 6.83 (dd, 1H, J = 8.8, 2.4 Hz, H-C(6)), 7.25-7.28 (m, 5H, ArH), 7.45 (d, 1H, J = 8.8 Hz, H-C(5)), 7.48-7.51 (m, 2H, ArH), 7.60-7.65 (m, 2H, ArH), 8.01 (d, 1H, J = 9.6 Hz, H-C(4)), 8.02 -8.03 (m, 1H, ArH). 13C NMR (100 MHz, CDCl3): δ 49.19 (C(1¢)), 70.65 (CH2O), 100.38, 110.55, 115.48, 118.30, 127.68, 128.41, 128.50, 128.94, 129.17, 130.67, 134.29, 135.07, 136.28, 139.98, 141.38, 161.21, 162.77 (C(2)), 192.65 (C(2¢)). Anal. Calcd for C24H19NO3: C, 78.03; H, 5.18; N, 3.79. Found: C, 78.00; H, 5.21; N, 3.79.

19b: 13 % yield. Mp 146-147 oC. 1H NMR (400 MHz, CDCl3): δ 5.12 (s, 2H, CH2O), 5.77 (s, 2H, H-C(1¢)), 6.97 (d, 1H, J = 9.6 Hz, H-C(3)), 7.10 (dd, 1H, J = 8.8, 2.4 Hz, H-C(6)), 7.17 (d, 1H, J = 2.4 Hz, H-C(8)), 7.32-7.42 (m, 3H, ArH), 7.44-7.47 (m, 2H, ArH), 7.51-7.55 (m, 2H, ArH), 7.61-7.66 (m, 2H, ArH), 7.97 (d, 1H, J = 8.8 Hz, H-C(5)), 8.06-8.09 (m, 1H, ArH), 8.07 (d, 1H, J = 9.6 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 67.83 (C(1¢)), 70.29 (CH2O), 107.91, 110.38, 117.04, 120.62, 127.88, 128.23, 128.33, 128.75, 128.86, 128.93, 129.01, 133.78, 135.30, 136.80, 139.19, 160.35, 161.51 (C(2)), 194.75 (C(2¢)). Anal. Calcd for C24H19NO3: C, 78.03; H, 5.18; N, 3.79. Found: C, 78.40; H, 5.26; N, 3.71.

7-Chloro-1-(2-oxo-2-phenylethyl)quinolin-2(1H)-one (20a) and 7-Chloro-2-(2-oxo-2-phenylethoxy)quinoline (20b)

Prepared from 7-chloroquinolin-2(1H)-one and 2-bromoacetophenone by the same procedure as described for 13a and 13b. 20a: 87 % yield. Mp 180-181 oC. 1H NMR (400 MHz, CDCl3): δ 5.76 (s, 2H, H-C(1¢)), 6.75 (d, 1H, J = 9.2 Hz, H-C(3)), 6.97 (d, 1H, J = 2.0 Hz, H-C(8)), 7.19 (dd, 1H, J = 8.4, 2.0 Hz, H-C(6)), 7.52 (d, 1H, J = 8.4 Hz, H-C(5)), 7.55-7.59 (m, 2H, ArH), 7.66-7.71 (m, 1H, ArH), 7.72 (d, 1H, J = 9.2 Hz, H-C(4)), 8.09-8.12 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3): δ 49.05 (C(1¢)), 114.37, 119.51, 121.49, 123.10, 128.46, 129.27, 130.34, 134.48, 134.87, 137.21, 139.57, 140.71, 162.15 (C(2)), 192.04 (C(2¢)). Anal. Calcd for C17H12NO2Cl0.2H2O: C, 67.76; H, 4.14; N, 4.65. Found: C, 67.92; H, 4.02; N, 4.66.

20b: 7 % yield. Mp 106-107 oC. 1H NMR (400 MHz, CDCl3): δ 5.76 (s, 2H, H-C(1¢)), 7.10 (d, 1H, J = 8.8 Hz, H-C(3)), 7.32 (dd, 1H, J = 8.4, 2.0 Hz, H-C(6)), 7.51-7.55 (m, 2H, ArH), 7.62-7.66 (m, 1H, ArH), 7.64 (d, 1H, J = 8.4 Hz, H-C(5)), 7.70 (d, 1H, J = 2.4 Hz, H-C(8)), 8.01 (d, 1H, J = 8.8 Hz, H-C(4)), 8.03-8.06 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3): δ 67.94 (C(1¢)), 113.26, 123.99, 125.46, 126.65, 128.16, 128.79, 129.10, 133.94, 135.07, 135.65, 139.29, 146.75, 161.66 (C(2)), 194.31 (C(2¢)). Anal. Calcd for C17H12NO2Cl: C, 68.58; H, 4.06; N, 4.70. Found: C, 68.22; H, 4.05; N, 4.64.

8-Methoxy-2-(2-oxo-2-phenylethoxy)quinoline (22b)

Prepared from 8-methoxyquinolin-2(1H)-one and 2-bromoacetophenone by the same procedure as described for 13a and 13b. 75 % yield. Mp 161-162 oC. 1H NMR (400 MHz, CDCl3): δ 3.88 (s, 3H, MeO), 5.80 (s, 2H, H-C(1¢)), 6.99-7.01 (m, 1H, ArH), 7.14 (d, 1H, J = 8.8 Hz, H-C(3)), 7.27-7.34 (m, 2H, ArH), 7.49-7.54 (m, 2H, ArH), 7.59-7.63 (m, 1H, ArH), 8.03 (d, 1H, J = 8.8 Hz, H-C(4)), 8.07-8.10 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3): δ 56.17 (MeO), 67.53 (C(1¢)), 109.54, 113.16, 119.66, 124.34, 126.55, 128.13, 128.65, 133.37, 135.46, 137.48, 139.42, 154.14, 160.16 (C(2)), 194.94 (C(2¢)). Anal. Calcd for C18H15NO3: C, 73.71; H, 5.15; N, 4.78. Found: C, 73.64; H, 5.19; N, 4.80.

8-Benzyloxy-2-(2-oxo-2-phenylethoxy)quinoline (23b)

Prepared from 8-benzyloxyquinolin-2(1H)-one and 2-bromoacetophenone by the same procedure as described for 13a and 13b. 91 % yield. Mp 132-133 oC. 1H NMR (400 MHz, CDCl3): δ 5.16 (s, 2H, CH2O), 5.86 (s, 2H, H-C(1¢)), 7.07 (d, 1H, J = 8.8 Hz, H-C(3)), 7.15-7.28 (m, 5H, ArH), 7.33-7.37 (m, 3H, ArH), 7.44-7.48 (m, 2H, ArH), 7.59-7.62 (m, 1H, ArH), 8.02-8.06 (m, 2H, ArH), 8.05 (d, 1H, J = 8.8 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 67.81 (C(1¢)), 71.38 (CH2O), 112.83, 113.26, 120.62, 124.48, 126.94, 127.16, 127.72, 128.15, 128.53, 128.71, 129.02, 133.71, 135.27, 137.61, 139.65, 153.42, 160.31 (C(2)), 194.62 (C(2¢)). Anal. Calcd for C24H19NO3: C, 78.03; H, 5.18; N, 3.79. Found: C, 78.01; H, 5.17; N, 3.61.

8-Chloro-2-(2-oxo-2-phenylethoxy)quinoline (24b)

Prepared from 8-chloroquinolin-2(1H)-one and 2-bromoacetophenone by the same procedure as described for 13a and 13b. 94 % yield. Mp 183-184 oC. 1H NMR (400 MHz, CDCl3): δ 5.80 (s, 2H, H-C(1¢)), 7.16 (d, 1H, J = 8.8 Hz, H-C(3)), 7.24-7.28 (m, 1H, ArH), 7.49-7.53 (m, 2H, ArH), 7.59-7.67 (m, 3H, ArH), 8.04-8.07 (m, 2H, ArH), 8.05 (d, 1H, J = 8.8 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 67.73 (C(1¢)), 113.54, 124.25, 126.33, 126.58, 127.99, 128.74, 129.74, 131.44, 133.50, 135.28, 139.69, 142.38, 161.01 (C(2)), 194.45 (C(2¢)). Anal. Calcd for C17H12NO2Cl: C, 68.58; H, 4.06; N, 4.70. Found: C, 68.42; H, 4.11; N, 4.81.

1-(2-Oxopropyl)quinolin-2(1H)-one (25a) and 2-(2-Oxopropoxy) quinoline (25b)

Prepared from quinolin-2(1H)-one and chloroacetone by the same procedure as described for 13a and 13b. 25a: 67 % yield. Mp 108-109 oC. 1H NMR (400 MHz, CDCl3): δ 2.24 (s, 3H, Me), 5.11 (s, 2H, H-C(1¢)), 6.73 (d, 1H, J = 9.6 Hz, H-C(3)), 7.00-7.24 (m, 2H, ArH), 7.51-7.58 (m, 2H, ArH), 7.74 (d, 1H, J = 9.6 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 27.06 (Me), 52.03 (C(1¢)), 113.69, 120.69, 121.20, 122.51, 129.12, 130.90, 139.30, 139.95, 161.89 (C(2)), 202.49 (C(2¢)). Anal. Calcd for C12HnNO2: C, 71.63; H, 5.51; N, 6.96. Found: C, 71.66; H, 5.51; N, 6.94.

25b: 10 % yield. Oily. 1H NMR (200 MHz, CDCl3): δ 2.27 (s, 3H, Me), 5.04 (s, 2H, H-C(1¢)), 7.03 (d, 1H, J = 8.8 Hz, H-C(3)), 7.39-7.61 (m, 2H, ArH), 7.71-7.79 (m, 2H, ArH), 8.04 (d, 1H, J = 9.0 Hz, H-C(4)). 13C NMR (50 MHz, CDCl3): δ 26.45 (Me), 70.07 (C(1¢)), 112.54, 124.44, 125.40, 127.29, 127.42, 129.64, 139.35, 146.00, 160.61 (C(2)), 204.89 (C(2¢)). Anal. Calcd for C12H11NO2: C, 71.63; H, 5.51; N, 6.96. Found: C, 71.33; H, 5.71; N, 6.83.

6-Methoxy-1-(2-oxopropyl)quinolin-2(1H)-one (27a) and 6-Methoxy-2-(2-oxopropoxy)quinoline (27b)

Prepared from 6-methoxyquinolin-2(1H)-one and chloroacetone by the same procedure as described for 13a and 13b. 27a: 56 % yield. Mp 171-172 oC. 1H NMR (400 NHz, CDCl3): δ 2.22 (3H, s, Me), 3.85 (s, 3H, MeO), 5.09 (s, 2H, H-C(1¢)), 6.74 (d, 1H, J = 9.6 Hz, H-C(3)), 6.94 (d, 1H, J = 9.2 Hz, H-C(8)), 7.03 (d, 1H, J = 2.8 Hz, H-C(5)), 7.13 (dd, 1H, J = 9.2, 2.8 Hz, H-C(7)), 7.68 (d, 1H, J = 9.6 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 27.11 (Me), 52.24 (C(1¢)), 55.74 (MeO), 111.02, 115.05, 119.48, 121.50, 121.82, 133.82, 139.48, 155.00, 161.53 (C(2)), 202.78 (C(2¢)). Anal. Calcd for C13H13NO3: C, 67.52; H, 5.67; N, 6.06. Found: C, 67.64; H, 5.75; N, 6.03.

27b: 7 % yield. Mp 78-79 oC. 1H NMR (400 MHz, CDCl3): δ 2.25 (s, 3H, Me), 3.89 (s, 3H, MeO), 5.00 (s, 2H, H-C(1¢)), 7.00 (d, 1H, J = 8.8 Hz, H-C(3)), 7.05 (d, 1H, J = 2.8 Hz, H-C(5)), 7.27 (dd, 1H, J = 9.2, 2.8 Hz, H-C(7)), 7.68 (d, 1H, J = 9.2 Hz, H-C(8)), 7.95 (d, 1H, J = 8.8 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 26.42 (Me), 55.51 (MeO), 70.08 (C(1¢)), 106.15, 112.61, 121.31, 125.97, 128.48, 138.36, 141.29, 156.37, 159.29 (C(2)), 205.07 (C(2¢)). Anal. Calcd for C13H13NO3: C, 67.52; H, 5.67; N, 6.06. Found: C, 67.50; H, 5.66; N, 6.06.

6-Benzyloxy-1-(2-oxopropyl)quinolin-2(1H)-one (28a) and 6-Benzyloxy-2-(2-oxopropoxy)quinoline (28b)

Prepared from 6-benzyloxyquinolin-2(1H)-one and chloroacetone by the same procedure as described for 13a and 13b. 28a: 71 % yield. Mp 184-185 oC. 1H NMR (400 MHz, CDCl3): δ 2.22 (s, 3H, Me), 5.09 (s, 2H, CH2O), 5.10 (s, 2H, H-C(1¢)), 6.73 (d, 1H, J = 9.2 Hz, H-C(3)), 6.94 (d, 1H, J = 9.2 Hz, H-C(8)), 7.10 (d, 1H, J = 2.8 Hz, H-C(5)), 7.20 (dd, 1H, J = 9.2, 2.8 Hz, H-C(7)), 7.33-7.45 (m, 5H, ArH), 7.66 (1H, d, J = 9.6 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 27.39 (Me), 52.44 (C(1¢)), 70.80 (CH2O), 112.54, 115.30, 120.37, 121.70, 122.02, 127.71, 128.45, 128.95, 134.16, 136.67, 139.75, 154.31, 161.77 (C(2)), 202.98 (C(2¢)). Anal. Calcd for C19H17NO3: C, 74.25; H, 5.58; N, 4.56. Found: C, 74.16; H, 5.57; N, 4.52.

28b: 10 % yield. Mp 115-116 oC. 1H NMR (400 MHz, CDCl3): δ 2.26 (s, 3H, Me), 5.01 (s, 2H, CH2O), 5.15 (s, 2H, H-C(1¢)), 7.01 (d, 1H, J = 8.8 Hz, H-C(3)), 7.14 (d, 1H, J = 2.8 Hz, H-C(5)), 7.33-7.43 (m, 3H, ArH), 7.36 (dd, 1H, J = 9.2, 2.8 Hz, H-C(7)), 7.47-7.48 (m, 2H, ArH), 7.70 (d, 1H, J = 9.2 Hz, H-C(8)), 7.94 (d, 1H, J = 8.8 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 26.72 (Me), 70.28 (C(1¢)), 70.56 (CH2O), 107.83, 112.93, 114.14, 121.99, 126.20, 127.77, 128.34, 128.89, 136.94, 138.64, 141.74, 155.74, 159.63 (C(2)), 205.45 (C(2¢)). Anal. Calcd for C19H17NO3: C, 74.25; H, 5.58; N, 4.56. Found: C, 74.44; H, 5.60; N, 4.55.

6-Chloro-1-(2-oxopropyl)quinolin-2(1H)-one (29a) and 6-Chloro-2-(2-oxopropoxy)quinoline (29b)

Prepared from 6-chloroquinolin-2(1H)-one and chloroacetone by the same procedure as described for 13a and 13b. 29a: 85 % yield. Mp 178-179 oC. 1H NMR (400 MHz, CDCl3): δ 2.27 (s, 3H, Me), 5.10 (s, 2H, H-C(1¢)), 6.76 (d, 1H, J = 9.6 Hz, H-C(3)), 6.92 (d, 1H, J = 9.2 Hz, H-C(8)), 7.44 (dd, 1H, J = 9.2, 2.0 Hz, H-C(7)), 7.56 (d, 1H, J = 2.0 Hz, H-C(5)), 7.65 (d, 1H, J = 9.6 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 27.22 (Me), 52.07 (C(1¢)), 115.24, 121.71, 122.53, 128.01, 128.21, 130.83, 137.90, 138.80, 161.48 (C(2)), 201.79 (C(2¢)). Anal. Calcd for C12H10NO2Cl: C, 61.16; H, 4.28; N, 5.94. Found: C, 61.13; H, 4.32; N, 6.01.

29b: 9 % yield. Mp 108-109 oC. 1H NMR (400 MHz, CDCl3): δ 2.26 (s, 3H, Me), 5.03 (s, 2H, H-C(1¢)), 7.06 (d, 1H, J = 8.8 Hz, H-C(3)), 7.54 (dd, 1H, J = 8.8, 2.0 Hz, H-C(7)), 7.69 (d, 1H, J = 8.8 Hz, H-C(8)), 7.70 (d, 1H, J = 2.8 Hz, H-C(5)), 7.95 (d, 1H, J = 8.8 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 26.42 (Me), 70.14 (C(1¢)), 113.64, 126.04, 126.25, 128.81, 129.91, 130.35, 138.42, 144.46, 160.84 (C(2)), 204.39 (C(2¢)). Anal. Calcd for C12H10NO2Cl: C, 61.16; H, 4.28; N, 5.94. Found: C, 61.18; H, 4.37; N, 5.93.

7-Methoxy-1-(2-oxopropyl)quinolin-2(1H)-one (30a) and 7-Methoxy-2-(2-oxopropoxy)quinoline (30b)

Prepared from 7-methoxyquinolin-2(1H)-one and chloroacetone by the same procedure as described for 13a and 13b. 30a: 84 % yield. Mp 113-114 oC. 1H NMR (400 MHz, CDCl3): δ 2.20 (s, 3H, Me), 3.84 (s, 3H, MeO), 5.05 (s, 2H, H-C(1¢)), 6.44 (d, 1H, J = 2.0 Hz, H-C(8)), 6.56 (d, 1H, J = 9.6 Hz, H-C(3)), 6.81 (dd, 1H, J = 8.8, 2.0 Hz, H-C(6)), 7.48 (d, 1H, J = 8.8 Hz, H-C(5)), 7.66 (d, 1H, J = 9.6 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 27.30 (Me), 52.50 (C(1¢)), 55.83 (MeO), 98.87, 110.02, 115.15, 118.16, 130.79, 140.07, 141.20, 162.29, 162.51 (C(2)), 203.19 (C(2¢)). Anal. Calcd for C13H13NO3: C, 67.52; H, 5.67; N, 6.06. Found: C, 67.44; H, 5.68; N, 6.00.

30b: 8 % yield. Mp 96-97 oC. 1H NMR (400 MHz, CDCl3): δ 2.26 (s, 3H, Me), 3.92 (s, 3H, MeO), 5.01 (s, 2H, H-C(1¢)), 6.89 (d, 1H, J = 8.8 Hz, H-C(3)), 7.04 (dd, 1H, J = 8.8, 2.4 Hz, H-C(6)), 7.13 (d, 1H, J = 2.4 Hz, H-C(8)), 7.60 (d, 1H, J = 8.8 Hz, H-C(5)), 7.96 (d, 1H, J = 8.4 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 26.68 (Me), 55.71 (MeO), 70.40 (C(1¢)), 106.77, 109.98, 116.90, 120.44, 128.66, 139.25, 148.06, 161.33, 161.44 (C(2)), 205.58 (C(2¢)). Anal. Calcd for C13H13NO3: C, 67.52; H, 5.67; N, 6.06. Found: C, 67.20; H, 5.88; N, 5.93.

7-Benzyloxy-1-(2-oxopropyl)quinolin-2(1H)-one (31a) and 7-Benzyloxy-2-(2-oxopropoxy)quinoline (31b)

Prepared from 7-benzyloxyquinolin-2(1H)-one and chloroacetone by the same procedure as described for 13a and 13b. 31a: 62 % yield. Mp 103-104 oC. 1H NMR (400 MHz, CDCl3): δ 2.17 (s, 3H, Me), 5.02 (s, 2H, CH2O), 5.12 (s, 2H, H-C(1¢)), 6.51 (d, 1H, J = 2.4 Hz, H-C(8)), 6.58 (d, 1H, J = 9.6 Hz, H-C(3)), 6.89 (dd, 1H, J = 8.8, 2.4 Hz, H-C(6)), 7.35-7.44 (m, 5H, ArH), 7.49 (d, 1H, J = 8.8 Hz, H-C(5)), 7.66 (d, 1H, J = 9.6 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 27.31 (Me), 52.49 (C(1¢)), 70.68 (CH2O), 99.95, 110.81, 115.32, 118.30, 127.78, 128.61, 129.02, 130.79, 136.21, 140.05, 141.14, 161.35, 162.50 (C(2)), 202.99 (C(2¢)). Anal. Calcd for C19H17NO3: C, 74.25; H, 5.58; N, 4.56. Found: C, 74.27; H, 5.59; N, 4.54.

31b: 8 % yield. Mp 133-134 oC. 1H NMR (400 MHz, CDCl3): δ 2.26 (s, 3H, Me), 5.01 (s, 2H, CH2O), 5.18 (s, 2H, H-C(1¢)), 6.90 (d, 1H, J = 8.4 Hz, H-C(3)), 7.13 (dd, 1H, J = 8.8, 2.4 Hz, H-C(6)), 7.24 (d, 1H, J = 2.4 Hz, H-C(8)), 7.34-7.38 (m, 1H, ArH), 7.40-7.44 (m, 2H, ArH), 7.48-7.51 (m, 2H, ArH), 7.63 (d, 1H, J = 8.8 Hz, H-C(5)), 7.97 (d,1H, J = 8.4 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 26.72 (Me), 70.39 (C(1¢)), 70.47 (CH2O), 107.90, 110.12, 117.25, 120.59, 127.90, 128.38, 128.76, 128.89, 136.75, 139.29, 147.96, 160.48, 161.43 (C(2)), 205.54 (C(2¢)). Anal. Calcd for C19H17NO3: C, 74.25; H, 5.58; N, 4.56. Found: C, 74.24; H, 5.57; N, 4.53.

7-Chloro-1-(2-oxopropyl)quinolin-2(1H)-one (32a) and 7-Chloro-2-(2-oxopropoxy)quinoline (32b)

Prepared from 7-chloroquinolin-2(Lf/)-one and chloroacetone by the same procedure as described for 13a and 13b. 32a: 76 % yield. Mp 158-159 oC. 1H NMR (400 MHz, DMSO-d6): δ 2.31 (s, 3H, Me), 5.23 (s, 2H, H-C(1¢)), 6.65 (d, 1H, J = 9.2 Hz, H-C(3)), 7.31 (dd, 1H, J = 8.4, 1.6 Hz, H-C(6)), 7.51 (d, 1H, J = 1.6 Hz, H-C(8)), 7.77 (d, 1H, J = 8.4 Hz, H-C(5)), 7.98 (d, 1H, J = 9.6 Hz, H-C(4)). 13C NMR (100 MHz, DMSO-d6): δ 28.10 (Me), 52.34 (C(1¢)), 115.06, 119.51, 121.46, 122.98, 131.22, 136.41, 140.27, 141.09, 161.56 (C(2)), 202.86 (C(2¢)). Anal. Calcd for C12H10NO2Cl: C, 61.16; H, 4.28; N, 5.94. Found: C, 61.09; H, 4.25; N, 5.96.

32b: 8 % yield. Mp 93-94 oC. 1H NMR (400 MHz, CDCl3): δ 2.27 (s, 3H, Me), 5.04 (s, 2H, H-C(1¢)), 7.03 (d, 1H, J = 8.8 Hz, H-C(3)), 7.35 (dd, 1H, J = 8.4, 2.0 Hz, H-C(6)), 7.65 (d, 1H, J = 8.4 Hz, H-C(5)), 7.79 (d, 1H, J = 1.6 Hz, H-C(8)), 8.12 (d, 1H, J = 8.8 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 26.67 (Me), 70.62 (C(1¢)), 113.02, 123.95, 125.69, 126.51, 128.84, 135.94, 139.55, 146.51, 161.53 (C(2)), 204.19 (C(2¢)). Anal. Calcd for C12H10NO2Cl: C, 61.16; H, 4.28; N, 5.94. Found: C, 61.19; H, 4.28; N, 5.93.

8-Methoxy-2-(2-oxopropoxy)quinoline (34b)

Prepared from 8-methoxyquinolin-2(1H)-one and chloroacetone by the same procedure as described for 13a and 13b. 67 % yield. Mp 55-56 oC. 1H NMR (400 MHz, CDCl3): δ 2.33 (s, 3H, Me), 4.01 (s, 3H, MeO), 5.09 (s, 2H, H-C(1¢)), 7.03-7.05 (m, 1H, ArH), 7.07 (d, 1H, J = 8.8 Hz, H-C(3)), 7.31-7.34 (m, 2H, ArH), 8.02 (d, 1H, J = 8.8 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 26.84 (Me), 56.20 (MeO), 69.95 (C(1¢)), 109.38, 112.88, 119.60, 124.44, 126.51, 137.40, 139.50, 154.17, 159.96 (C(2)), 204.66 (C(2¢)). Anal. Calcd for C13H13NO3: C, 67.52; H, 5.67; N, 6.06. Found: C, 67.51; H, 5.73; N, 5.90.

8-Benzyloxy-2-(2-oxopropoxy)quinoline (35b)

Prepared from 8-benzyloxyquinolin-2(1H)-one and chloroacetone by the same procedure as described for 13a and 13b. 75 % yield. Mp 56-57 oC. 1H NMR (400 MHz, CDCl3): δ 2.15 (s, 3H, Me), 5.00 (s, 2H, CH2O), 5.24 (s, 2H, H-C(1¢)), 7.06 (d, 1H, J = 8.8 Hz, H-C(3)), 7.09-7.11 (m, 1H, ArH), 7.25-7.42 (m, 5H, ArH), 7.52-7.54 (m, 2H, ArH), 8.02 (d, 1H, J = 8.8 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 26.52 (Me), 69.84 (C(1¢)), 71.07 (CH2O), 111.76, 112.72, 120.08, 124.31, 126.60, 127.49, 127.86, 128.45, 137.20, 137.83, 139.39, 153.27, 159.81 (C(2)), 204.48 (C(2¢)). Anal. Calcd for C19H17NO3: C, 74.25; H, 5.58; N, 4.56. Found: C, 74.27; H, 5.71; N, 4.38.

8-Chloro-2-(2-oxopropoxy)quinoline (36b)

Prepared from 8-chloroquinolin-2(1H)-one and chloroacetone by the same procedure as described for 13a and 13b. 89 % yield. Mp 99-100 oC. 1H NMR (400 MHz, CDCl3): δ 2.33 (s, 3H, Me), 5.09 (s, 2H, H-C(1¢)), 7.10 (d, 1H, J = 8.8 Hz, H-C(3)), 7.30 (dd, 1H, J = 7.6, 7.6 Hz, H-C(6)), 7.64 (dd, 1H, J = 8.0, 1.2 Hz, H-C(7)), 7.72 (dd, 1H, J = 7.6, 1.2 Hz, H-C(5)), 8.05 (d, 1H, J = 8.8 Hz, H-C(4)). 13C NMR (100 MHz, CDCl3): δ 26.72 (Me), 70.16 (C(1¢)), 113.35, 124.35, 126.37, 126.58, 129.86, 131.44, 139.75, 142.33, 160.89 (C(2)), 203.87 (C(2¢)). Anal. Calcd for C12H10NO2Cl: C, 61.16; H, 4.28; N, 5.94. Found: C, 61.17; H, 4.23; N, 5.98.

 

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