A volatile organic solvent‐free deep eutectic solvent (DES) was prepared by utilizing 1 : 10 ratio of potassium carbonate (PC) as a hydrogen bond acceptor (HBA) and ethylene glycol (EG) as a hydrogen bond donor (HBD). Subsequently, DES was utilized as a solvent in the Pd‐catalyzed Suzuki‐Miyaura or Sonogashira cross‐coupling reactions of boronic acids or acetylenes respectively with in situ generated 2‐bromobenzo[2,3][1,4]oxazepino[7,6‐b]quinoline, 3 The anhydrous conditions without air exclusion, low catalyst loading, low toxicity, high efficiency, low cost, and bioavailability are the advantages of DES in C−C bond forming reactions. Moreover, a gram‐scale reaction under mild conditions with an excellent yield was productive. The one‐pot reaction of 6‐bromo‐2‐chloroquinoline‐3‐carbaldehyde, 1 through 2‐bromobenzo [2,3][1,4]oxazepino [7,6‐b]quinoline, 3 intermediate, and subsequent Suzuki‐Miyaura or Sonogashira coupling was successfully attempted.
All reactions were carried out under argon atmosphere. The THF, Toluene and Acetone were purchased from Rankem Laboratories in 500 mL bottles. 6-Bromo 2-chloro-3-formylquinoline was purchased from Sigma-Aldrich Chemicals, 1, 3-cyclohexanedione and Potassium Phosphate tribasic was purchased from Aldrich Chemical Co. Both THF and deionized water were degassed by performing evacuation / Argon refill cycles and stored under Argon prior to use. All the aryl boronic acids (Table 2) were purchased from Frontier Scientific, Aldrich Chemical Co., Alfa-Aesar, Combi-Blocks and used as received without further purification. All the halides (Table 3) was purchased from Aldrich Chemical Co., Alfa-Aesar and used as received without further purification. The ligand XPhos and the catalyst Pd(OAc) 2 was purchase from Johnson Matthey Chemicals. Flash Chromatography was performed using a Biotage SP4 instrument with prepacked silica cartridges.
General Analytical InformationAll compounds were characterized by 1 H NMR, 13 C NMR and LC-MS spectroscopy, copies of the 1 H and 13 C NMR spectra can be found at the end of the Supporting Information. The proton ( 1 H) and carbon ( 13 C) NMR spectra were recorded on a Bruker 400 MHz instrument using TMS as an internal standard. All the 1H NMR experiments are reported in δ units, parts per million (ppm), and were measured relative to the signals for residual DMSO (2.50) in the deutrated solvent. All the 13 C NMR spectra were reported in ppm relative to DMSO-d6 (40.01 ppm), and all were obtained with 1 H decoupling. All the LC-MS spectra were obtained using Atlantis dC 18 and Zorbax XDBC 18 Columns
Experimental Sections
Synthesis of Precatalyst 1A mixture of Pd(OAc) 2 (1.69 g, 7.5 mmol) and 2-amino-biphenyl (1.32 g, 7.8 mmol) in anhydrous toluene (45 mL) was heated at 60 °C under argon for 30 min, at which point the initial red color of the solution became grey precipitate had formed. After the reaction cooled at room temperature, the toluene was removed via canula. The remaining solid was washed with anhydrous toluene (2 X 20mL) and then suspended in anhydrous acetone (45 mL). After addition of lithium chloride (0.96 g, 22.5 mmol), the resulting slurry was stirred at room temperature under argon for 1 h to give a homogenous green solution. XPhos (3.38 g, 7.12 mmol) was then added portion wise over 5 min. The mixture was stirred at room temperature for 2.5 h, at which point a significant amount of precipitate had formed. Removal of about 90% of the solvent under vacuum afforded yellow slurry, which was treated with MTBE (10 mL) and pentane (25 mL). The mixture was then placed in a refrigerator for 1 h. At this point, the product was collected by suction filtration, washed with water (3 X 10 mL), and dried under vacuum to afford off white solid. Yield: 5 g (85%).
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