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Intermediate B (200mg, 1.01mml) was stirred in MeOH (10ml) at r.t. under N2 and 2- napthaldehyde (148mg, 0.96mmol) was added. The resultant solution was stirred for 3 h. After this time, NaBH4 (61 mg, 1.62mmol) was added, causing fizzing, and the solution stirred for 10 min. 1 M NaOH (20ml) was then added, forming an opaque white solution which was stirred for 20 min. H2O (50ml) was then added and the solution extracted with Et2O (2 x 100ml). The combined organic extracts were dried (MgSO4) and solvent removed in vacuo to give the title compound as a colourless oil (320mg, 100%). LCMS purity 98%, m/z 339 [M+H]+.
With hydroxylamine hydrochloride; caesium carbonate; In water; dimethyl sulfoxide; at 125℃; for 48h;
General procedure: Aldehyde (0.5mmol), NH2OH·HCl (0.6mmol) and Cs2CO3 (0.6mmol) were stirred at 125C for 48h in a 3:1 mixture of DMSO-H2O (2mL) under air. The progress of the reaction was monitored by TLC using ethyl acetate and hexane as eluent. After completion, the reaction mixture was cooled to room temperature and treated with water (1mL). The resulting mixture was extracted with ethyl acetate (3×5mL). Drying (Na2SO4) and evaporation of the solvent gave a residue that was purified on silica gel column chromatography using ethyl acetate and hexane. The purified products were identified by 1H NMR spectra and the melting points comparison with the literature data.
77%
With C49H54Cl2Ir2N2O6; hydroxylamine hydrochloride; sodium hydrogencarbonate; In toluene; at 110℃; for 12h;Inert atmosphere; Schlenk technique;
General procedure: The complexes (1-3) (0.002mmol), the aldehyde (1mmol), NH2OH·HCl (1mmol) and NaHCO3 (1mmol) were introduced in a dried schlenk tube and purged with N2. Then, to the mixture, dried and degassed toluene (2mL) was added, and the solution was refluxed for 12h. The mixture was cooled to room temperature and the products were extracted with methanol and dichloromethane before being filtered through Celite to remove the remaining complex. The amide was purified using column chromatography, and dried under vacuum. Characterization details for each amide are given in the Supporting information.
74%
With hydroxylamine hydrochloride; caesium carbonate; In acetonitrile; at 60 - 65℃;
General procedure: To a stirred solution of acetonitrile (10 mL), aldehyde (1.0 mmol) and bioglycerol-based carbon catalyst (10 wt %) were added and stirred for 10 min. To this NH2OH·HCl (1.0 mmol) followed by Cs2CO3 (1.0 mmol) were added, after which the reaction mixture was heated at 60-65 C until completion of the reaction as indicated by TLC. The reaction mixture was cooled to room temperature and catalyst was filtered, the solvent was removed by rotary evaporator. The crude residue was extracted with ethyl acetate (3 × 10 mL). The combined organic layers were extracted with water, saturated brine solution, and dried over anhydrous Na2SO4. The organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography using ethyl acetate and hexane (2:8) as eluents to give the corresponding substituted benzamide derivative in (71-78%) yield. The identity and purity of the product were confirmed by 1H, 13C NMR, and mass spectra.
72%
With hydroxylamine; copper diacetate; In water; at 110℃; for 48h;
General procedure: To a solution of copper(II) acetate (0.04 mmol) in water (1 mL) were added the corresponding aldehyde (3, 2 mmol) and the hydroxylamine (4, 2 mmol). After 2 days stirring at 110 C the mixture was quenched with a saturated solution of ammonium chloride (10 mL), or added ether (2 mL) for the recycling process. The mixture was extracted with AcOEt (3×10 mL) and washed with brine (10 mL), after drying with anhydrous MgSO4, the organic layer was filtered on Celite and the solvents were removed under low pressure (15-18 Torr). The product was purified recrystallization from chloroform/hexane mixtures to give the corresponding product 2. Amides 2a,262b,272c, 272d,172e,282f,292g,272h,172j,302k,172l30 and 2m17 are commercially available and were characterized by comparison of their physical and spectroscopic data with those of pure examples. Yields are included in Table 4 (Fig. 1 for recycling processes). Physical and spectroscopic data, as well as literature data for known compounds, follow.
With C33H27ClN3OPRu; hydroxylamine hydrochloride; sodium hydrogencarbonate; In toluene; at 20 - 110℃; for 8.25h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: The reaction vessel was charged with aldehyde (1mmol), NH2OH·HCl (1 mmol), NaHCO3 (1 mmol),[Ru-NHC] catalyst (0.5 mol %) and the mixture wasplaced under an atmosphere of N2. About 2 mL of dryand degassed toluene was added and the mixture wasstirred for 15 min at room temperature followed byreflux for 8 h. On completion of the reaction, 2-3 mLmethanol was added to the mixture followed by filtrationthrough Celite to remove the catalyst and NaHCO3.The crude product was then purified by column chromatography(MeOH/CH2Cl2, 1:1) using silica (200-400 mesh) as solid phase provided the amide in goodyield. The resultant amide solution was subjected to GCanalysis and the product was identified in comparisonwith authentic samples
85%Chromat.
With C23H27Cl2N3Rh(1+)*C24H20B(1-); hydroxylamine hydrochloride; sodium hydrogencarbonate; In toluene; at 110℃; for 2h;Inert atmosphere; Schlenk technique;
General procedure: Compound 3 (0.002 mmol), the aldehyde (1 mmol), NH2OHHCl(1 mmol) and NaHCO3 (1 mmol) were introduced in a dried schlenktube and purged with N2. Then, to the mixture, dried and degassedtoluene (2 ml) was added and the mixture was stirred for about10 min at room temperature, before the solution was refluxed understirring for 2 h. The mixture was cooled and the products wereextracted with methanol and dichloromethane before beingfiltered through celite to remove the remaining catalyst andNaHCO3. The crude amide was purified using column chromatography,and dried under vacuum.
With ammonium acetate; In butan-1-ol; at 120℃; for 12h;
General procedure: Aldehyde 1 (0.5 mmol), 3-cynaoacetyl indole 2 (0.5 mmol), and 3-amino-2-enone 3 (0.5 mmol) at 120 C was stirred for 8 h or 12 h in 2 mL n-BuOH in the presence of NH4OAc (0.5 mmol). After the completion (monitored by TLC), water (50 mL) was added. The mixture was filtered and the solid product was washed with water (3×5 mL). The crude product was purified by recrystallization from EtOH to give 4.
With ammonium acetate; In butan-1-ol; at 120℃; for 12h;
General procedure: Aldehyde 1 (0.5 mmol), 3-cynaoacetyl indole 2 (0.5 mmol), and 3-amino-2-enone 3 (0.5 mmol) at 120 C was stirred for 8 h or 12 h in 2 mL n-BuOH in the presence of NH4OAc (0.5 mmol). After the completion (monitored by TLC), water (50 mL) was added. The mixture was filtered and the solid product was washed with water (3×5 mL). The crude product was purified by recrystallization from EtOH to give 4.
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