| 89% |
With potassium hydroxide for 10h; Reflux; |
|
| 89% |
With potassium hydroxide at 60℃; |
1.1 General procedure for the synthesis of 2-methoxyquinoline-3-carbaldehydes (19-24)
To a solution of KOH (75.7 mmol) in MeOH (100 mL) was added the corresponding 2-chloro-3-quinolinecarbaldehyde (52.2 mmol) with constant stirring. The mixture was heated under reflux for 2.5-6 h and then cooled to room temperature. The product was precipitated out by adding water (300 mL) and then collected by vacuum filtration. The dried crude was recrystalised in DCM to afford compounds in yields ranging from 42-89%. 2-Methoxyquinoline-3-carbaldehyde (19) Yellow solid. Yield = 89%; M.p.: 96-98 °C; 1H NMR (300 MHz, CDCl3): δH = 10.46 (1H, s, CHO), 8.57 (1H, s, H-4), 7.88 - 7.82 (2H, m, H-5, H-8), 7.75 - 7.70 (1H, m, H-6), 7.45 - 7.39 (1H, m, H-7), 4.18 (3H, s, OCH3); 13C NMR (75 MHz, CDCl3): δC = 189.3, 161.2, 149.0, 140.0, 132.5, 129.7, 127.3, 125.0, 124.4, 120.1, 53.8. |
| 89% |
With potassium hydroxide Reflux; |
|
| 85% |
With potassium hydroxide for 3h; Reflux; |
|
| 85% |
With potassium hydroxide for 2.5h; Heating; |
|
| 80% |
With potassium hydroxide for 2.5h; Heating / reflux; |
2
EXAMPLE 2; Preparation of 2-Methoxy-quinoline-3-carboxaldehyde (4); To a solution of 5 g (75.7 mmol) of KOH in 100 ML OF MEOH was added 10 g (52.2 mmol) of 2-chloro-3-quinolinecarboxaldehyde. The mixture was heated to reflux for 2.5 h and then cooled to rt. To the solution was added 300 mL of water and the precipitated product collected by filtration to afford 7.82 g (80%) of 4 as a tan solid. An analytical sample could be prepared by recrystallization from CH2CL2/HEXANES : mp 92-93 °C ; 'H NMR (CDCL3, 400 MHz) 8 4.14 (s, 3H), 7. 37 (dd, 1H, J = 8.0 and 6.9 Hz), 7.67 (M, 1H), 7.76 (d, 1H, J = 8.0 Hz), 7.80 (d, 1H, J = 8.4 HZ), 8.48 (s, 1H), 10.40 (s, 1H) ; 13C NMR (CDCL3, 100 MHz) 8 53.8, 120.0, 124.4, 125.0, 127.3, 129.7, 132.5, 139.9, 148.9, 161.1, 189.2 ; Anal. Calcd. FOR CLLH9NO2 : C, 70.58 ; H, 4.85 ; N, 7.48. Found: C, 70.44 ; H, 4.70 ; N, 7.39. |
| 70% |
With sodium carbonate at 65℃; for 4h; |
Typical experimental procedure:
General procedure: To a stirred solution of substrate (1 mmol, arylhalide/olefinic halide) in suitable alcohol (MeOH/EtOH, 10 mL), sodiumcarbonate (1.06 g, 2 mol %) was added and the reaction mixture was refluxed(MeOH = 65 C/EtOH = 78 C) for specified time. On completion, the reactionmixture was filtered, washed with methanol and dried in vacuo. The residuewas taken in ethyl acetate (20 mL) and washed with water. Organic layer wasdried over anhydrous sodium sulfate and evaporated in vacuo. The residuethus obtained was purified through Flash chromatography using ethyl acetate-hexane system. All the compounds were characterized and confirmed bycomparison of their spectral data and physical properties with reportedliterature |
| 57% |
With potassium hydroxide at 100 - 110℃; for 3h; |
General procedure for the synthesis of 6-substituted-2-methoxyquinoline-3-carbaldehydes 3a-d
General procedure: To a solutionof potassium hydroxide (1 g, 0.00178 mol) in 50 mL ofmethanol was added 6-substituted-2-chloroquinoline-3-carbaldehydes 2a-d (0.0131 mol). The mixture washeated cautiously at 100-110 °C for 3 h. After completionof the reaction, the resulting mixture was then cooled andpoured onto 200 g of crushed ice. The solid productobtained was filtered, washed with water, dried and purifiedby column chromatography (Pet. ether/Ethyl acetate 8:2). |
|
With potassium hydroxide Reflux; |
|
|
With potassium hydroxide Reflux; |
|
|
With sodium methylate at 60 - 70℃; |
|
|
With potassium carbonate for 6h; Reflux; |
|
|
With potassium hydroxide Reflux; |
2-Methoxy-3-formylquinolines (1c and 1d).
General procedure: A modified method of Waghray et al.40 was used. Briefly, the 2-chloro-3-formylquinolines 1a (10.4 mmol) and 1b (10.4 mmol) were added to a solution of potassiumhydroxide (15.6 mmol) in methanol (100 mL) and the contents refluxed overnight. Upon completion, thereaction was cooled to room temperature and cold water added to precipitate the product, which was thenfiltered and dried. |
|
With sodium at 40℃; |
5.1.3 General procedure for preparation of 2-methoxyquinoline-3-carbaldehydes (4a-i)
General procedure: To solution of sodium metal (0.05g, 2mmol) in methanol (10mL) a suspension of 2-chloroquinoline-3-carbaldehydes 3a-i (1mmol) in methanol (10mL) was added within 10min. The mixture was stirred at 40°C for 3-6h, then the reaction left to cool, neutralized with few drops of acetic acid and then poured onto ice H2O. The products were dried and crystallized using ethyl acetate [54-60]. |
|
With potassium hydroxide at 100℃; |
General procedure for the synthesis of N’-substituted-2-chloroquinoline-3-carbaldehydes2(a-e) and N’-substituted-2-methoxyquinoline-3-carbaldehydes 5(a-e)
General procedure: Dimethylformamide 9.6 mL (0.125 mol) was takenin round bottom flask equipped with drying tube and phosphorus oxychloride 32.2 mL (0.35 mol) was added drop wise with continuous stirring at 0°C. To above solution different aryl acetanilide 1(a-e) (0.05 mol) were added and after 5 min the solution is heated under reflux for 16-17 h. The completion of the reaction was monitored by TLC, reaction contents were decanted into crushed ice with constant stirring. The settled solid was sieved, washed with water, dried and purified by recrystallization using ethyl acetate to afford final pure product 2(a-e) in good yield. Thus, obtained 2(a-e) (0.0131 mol) were refluxed at 100°C in a mixture containing 1 g of KOH (0.00178 mol) in 50 mL dried methanol for 2.5-3 h and then cooled to room temperature and decanted on crushed ice. The precipitated solid was sieved, washed with water, dried and purified by recrystallization from petroleum ether at 450 C. |
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