N-(3-Acetyl-4-hydroxyphenyl)acetamide

Acetyl chloride (25 ml, 0.352 mol) was added to a stirred suspension of 9 (20 g, 0.121 mol) in carbon disulfide (50 ml). Aluminum chloride (55 g, 0.412 mol) was added step by step. The mixture was then heated at 80-90 °C. After 90 min, the solvent was evaporated under vacuum. Crushed ice and water was added cautiously to the residue. The resulting precipitate was collected by filtration and washed with water. The crude product was then dissolved in an aqueous solution of sodium hydroxide 5percent (w/v) and filtered through Celite.(R).. The filtrate was then acidified to pH 1 by addition of concentrated hydrochloric acid. The title compound was collected by filtration, washed with water and dried (21.05 g, 90percent): mp: 162-164 °C; IR (KBr) ν: 3452 cmTo the suspension of /V-(4-methoxyphenyl)acetamide (20 g) in carbon disulfide (50 ml_) and acetyl chloride (25 ml_) was added aluminum chloride (55 g) portionwise. The reaction mixture was heated at 80-90°C for 90 min, then evaporated under reduced pressure. The residue was suspended in water and ice and the insoluble material was collected by filtration. The product was dissolved in a 5percent aqueous solution of sodium hydroxide. The solution was treated with charcoal, filtered and acidified with 12N HCI. The precipitate was collected by filtration, washed with water and dried (yield: 90percent); melting point: 162-164°C.To a stirring suspension of [N- (4-METHOXY-PHENYL)-] acetamide (5.253 g, 32 mmol) and acetyl chloride (6.6 ml, 93 mmol, 2.9 equ) in dichloromethane (55 ml) was added aluminium trichloride (14.55 g, 109 mmol, 3.4 equ) in portions over 90 minutes. The reaction was then heated to reflux for 4.5 hours and cooled overnight. The mixture was poured onto ice then extracted into dichloromethane (5x), dried [(MGSO4)] and concentrated in vacuo to give [N- (3-] acetyl-4-hydroxy-phenyl) -acetamide (5.336 g, [87 percent)] as a pale green solid. [H] nmr (400 MHz, CDC13) 2.19 (s, 3H) 2.63 (s, 3H) 6.94 (d, [1H, ] 9 Hz) 7.12 (brs, [1H, ] NH) 7.33 (dd, 1H, 2.6+9 Hz) 8.17 (d, 1H, 2.6 Hz) 12.12 (s, 1H). [13C] nmr (100 MHz, CDC13) 24.71 (CH3) 27.16 [(CH3)] 119.08 (CH) 119.60 (Q) 122.94 (CH) 129.58 (CH) 159.62 (Q) 168.86 (Q) 204.84 (Q). EI+ 193.1 [(100percent, M)] 151.1 (91percent, [[M-AC] +) CLOHLLNO3] Calc. [193.] 0739 Found 193.0740.Method AA. Preparation of Intermediate ll-F (Scheme 2). To a stirring suspension of Intermediate ll-E (32 mmol) and acetyl chloride (93 mmol) in DCM, aluminium trichloride (109 mmol) was added in portions over 90 min. The reaction was then heated to reflux for 4.5 h and cooled overnight. The mixture was poured onto ice, then extracted with DCM (5x), dried (MgS0Intermediate 2 (4.2 g, 0.025 mol) was dissolved in 120 mL of CHAluminium chloride (56.0 g, 420 mmol) was added in four portions over 45 min to a mixture of 4-acetamidoanisole (20.0 g, 121 mmol) and acetyl chloride (25.8 mL, 363 mmol) in dichloromethane (190 mL). The crude 2 (5.10 g, 30.87 mmol) was dissolved in dichloromethane(120 mL) with stirring and cooling, to which aluminiumchloride and acetyl chloride were added quickly. Then the mixture was heated to reflux for 12 h. After cooling to room temperature, the supernatant liquid of the mixture was poured into 100 mL ice-cold water, while the underlayer residue was stirred with 4percentaqueous HCl for another half an hour. The precipitate was filtratedthrough buchner funnel and dried to give a yellow-green solid of4.68 g (24.22 mmol, 78percent). To a suspension of paracetamol (1) (66.00 mmol) and anhydrousaluminium chloride (16.00 mmol) in nitrobenzene(50 mL) was added acetyl chloride (0.013 mol) over a periodof 0.5 h. The temperature was gradually raised to 130°C overa period of 0.5 h and then maintained for 2.5 h. The mixturewas then cooled to 40°C within 0.5 h and poured into a mixtureof 350 g crushed ice and 30 mL conc. hydrochloric acidwith vigorous stirring and filtered. The crude product thusobtained was washed with water till free from acid followedby toluene and crystallized from isopropanol to yield lightbrown needle shaped crystals of 5-acetamino-2-hydroxyacetophenone(2). Yield 81.50percent. mp 160–164°C.A mixture of 2-aminophenol (1) (1.0 mmol), acetic anhydride (2.2 mmol) and pyridine (3.0 mmol) was heated at 100°C for 2 h. The reaction mixture was poured into ice cold water, filtered, dried and recrystallized from hexane as colorless needles, mp 152°C ([9]: 159–160°C). The diacetyl derivative 2 (1.0 mmol) was mixed with anhydrous ZnCl2 (1.5 mmol) and heated to 180°C for 2 h. The reaction mixture was treated with ice cold water and concentrated HCl. The solid product was filtered off, dried and recrystallized from ethanol as pale yellow needles, mp 157°C ([9]: 159–160°C).

Molecular Weight:193.20
XLogP3:1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:193.07389321
Monoisotopic Mass:193.07389321
Topological Polar Surface Area:66.4
Heavy Atom Count:14
Complexity:240
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes