| 98% |
With polyvinylpolypyrrolidone supported triflic acid In neat (no solvent) at 20℃; for 0.05h; Green chemistry; |
General experimental procedure
General procedure: To a mixture of substrate (1.0 mmol) and acetic anhydride (1.0 mmol), 0.008 g PVPP.OTf (3.4 mol%) was added. The mixture was stirred at room temperature for the time indicated in Tables 2, 3 and 4. The progress of the reaction was followed by TLC or GC for aliphatic alcohols. After completion of the reaction, ethyl acetate (2 9 10 cm3) was added, and the catalyst was separated by filtration. The filtrate was washed with an aqueous solution of NaHCO3 (10%, 2 9 10 cm3) and water (2 9 10 cm3) and dried with Na2SO4. The solvent was evaporated under reduced pressure to afford the expected product. |
| 98% |
In dichloromethane at 20℃; for 0.25h; |
3.1. N-Phenylacetamide (11a)
General procedure: To aniline (7a, 930mg, 10mmol) dissolved in DCM (10ml), acetic anhydride (1122mg, 11mmol) was added while cooling. After addition the reaction mixture was stirred at room temperature for 15 min. After completion of the reaction water was added and the compound was extracted using DCM. The solvent was evaporated under reduced pressure to afford compound 11a in excellent yield (98%). |
| 98.6% |
In lithium hydroxide monohydrate at 50 - 70℃; |
21 Preparation of 4-acetamidoanisole
1000mL dried flask was added 55 g of acetic anhydride, warmed to 50 ° C, the control temperature at 50-70 ° C conditions, 50 g of p-aminoanisole was added in portions. Plus temperature insulation 10-20 minutes, HPLC to p-aminoanisole less than 0.1% is the end of the reaction. Add 50 g of water, cool to 10 ° C_15 ° C under stirring, suction filtration, the filter cake was washed with 10 g of water, dried to give 4-acetamidoanisole 66.06g, yield 98.6%, HPLC purity of 99.2%. |
| 98.6% |
at 50 - 70℃; |
21 Preparation of 4-acetamidoanisole
1000mL dried flask was added 55 g of acetic anhydride, warmed to 50 ° C, the control temperature at 50-70 ° C conditions, in batches Add 50 g p-aminoanisole. Plus temperature insulation 10-20 minutes, HPLC to p-aminoanisole less than 0.1% is the end of the reaction. Add 50 g of water, cool to 10 ° C_15 ° C under stirring, suction filtration, the filter cake was washed with 10 g of water, dried to give 4-acetamidoanisole 66.06g, yield 98.6%, HPLC purity 99.2%. |
| 98.6% |
at 50 - 70℃; |
20 Preparation of 4-acetamidoanisole
A 1000 mL dry flask was charged with 55 g of acetic anhydride,Warmed to 50 ,Control the temperature at 50-70 conditions,50 g para-aminoanisole was added in portions.Canada plus insulation 10-20 minutes,HPLC to para-amino-anisole less than 0.1% is the end of the reaction.Add 50 grams of water,Cooled to 10 -15 with stirring, suction filtered, the filter cake was washed with 10 g of water,Dried to give 4-acetamido anisole 66.06g, yield 98.6%HPLC purity 99.2%. |
| 97% |
With glacial acetic acid at 20℃; for 0.5h; |
|
| 96% |
With ZnAl2O4 nanoparticles at 20℃; for 0.05h; Neat (no solvent); |
|
| 96% |
In dichloromethane at 20℃; for 2h; Cooling with water; |
1; 2.a 4-Acetamidoanisole
Acetic anhydride (16.0 mL, 169 mmol) was added dropwise over 1 h to a mixture of p-anisidine (20.0 g, 162 mmol) and dichloromethane (60 mL), with moderation by cooling in a water bath. The mixture was stirred at room temperature for 1 h, during which time a solid formed. Petroleum spirit (190 mL) was added, and the mixture was stirred for a further 1 h. The mixture was filtered and washed with petroleum spirit to afford 4-acetamidoanisole as a pale grey solid (25.8 g, 96%), m.p. 127-128° C. 1H NMR (399.7 MHz, CDCl3) δ 2.13, 3.78 (2 s, 2*3H, 2*CH3); 6.83 (app. d, 2H, J=8.8 Hz, BB'); 7.38 (app. d, 2H, J=8.8 Hz, AA'); 7.59 (br s, 1H, NH). |
| 96% |
In neat (no solvent) at 20℃; for 0.05h; |
Catalytic tests
General procedure: Alcohol, phenol, and/or amine (1 mmol) were added to amixture of the ZnAl2O4SiO2 nanocomposite (100 mg) andacetic anhydride (1 mmol). The mixture was stirred at 75 °C(for alcohols and phenols) or at room temperature (for amines)for a time. The progress of the reaction was monitored by TLCand/or GC-MS. When the reaction was completed, ethyl acetate(10 mL) was added and the mixture was filtered to separate offthe catalyst. The catalyst was washed twice with 7.5 mL ethylacetate. The combined organic phases were washed with a10% solution of NaHCO3 and then dried over MgSO4. The solventwas removed to yield the product. If further purificationwas needed, the product was passed through a short column ofsilica gel. All products were characterized on the basis ofGC-MS, FT-IR, and 1H-NMR spectral data by comparing thesespectra with those of standard samples or literature data. |
| 95% |
In dichloromethane at 25℃; for 1.5h; |
|
| 95% |
In dichloromethane for 2h; |
|
| 95% |
In hexane; dichloromethane for 3h; |
11 [N- (4-METHOXY-PHENYL)-ACETAMIDE (51)]
To a stirring suspension of p-anisidine (6.036 g, 49 mmol) in dichloromethane (20 ml) was added acetic anhydride (5 ml, 53 mmol, 1.1 equ) over one hour. The reaction was stirred for a further hour then poured onto hexane (60 ml) and stirred for another hour. The solid was collected and washed with hexane to give [N- (4-METHOXY-PHENYL)-ACETAMIDE] 51 (7.717 g, 95%) as a pale grey solid. 1H nmr (400 MHz, CDCl3) 2.13 (s, 3H) 3.78 (s, 3H) 6.83 (d, 2H, 9 Hz) 7.38 [(D,] 2H, 9 Hz). 13C nmr [(100] MHz, CDCl3) 24.66 (CH3) 55.85 [(CH3)] 114.49 (CH) 122.37 (CH) 131. 41 [(Q)] 156.82 (Q) 168.79 (Q). EI+ 165.1 [(710,] [M+)] 123.1 (70%, [[M-AC] +)] 108.1 [(100%,] [NH2PhO]+) C9H11NO2 Calc. 165.0790 Found 165. 0789. |
| 95% |
With 1H-imidazole at 20℃; Green chemistry; |
In a typical procedure for the conversion of aniline into acetanilide
General procedure: aniline (1.0 mmol, 0.09 g) was added to a stirred mixture of acetic anhydride (2.0 mmol, 0.188 mL) and imidazole (0.08 mmol 0.005 g) at room temperature, and the progress of the reaction was monitored by TLC. Upon completion of the reaction (1 min), water (3 mL) was added to the mixture resulting in the precipitation of the acetanilide, which was collected by filtration and washed with water before being dried under vacuum at 70 °C to give the desired product in high purity as colorless crystals (0.128 g, 95% yield). 1H NMR (400 MHz, CDCl3): δ 2.17 (s, 3H), 7.12 (t, J=7.2 Hz, 1H), 7.31 (t, J=7.6 Hz, 2H), 7.54 (d, J=7.64 Hz, 2H), 8.21 (s, 1H). 13C (100 MHz, CDCl3): δ 24.4, 120.2, 124.3, 128.9, 138.1, 169.2. |
| 95% |
In dichloromethane for 2h; |
PREPARATION OF N-(4-Methoxy-phenyl)-acetamide.
To a stirring suspension of p-anisidine (6.036 g, 49 mmol) in DCM (20 mL), acetic anhydride (5 mL, 15 53 mmol) was added dropwise over a period of 1 h. The reaction was stirred for 1 h, then poured into hexane (60 mL) and stirred for further 1 h. The solid formed was collected by filtration and washed with hexane to afford the title compound (7.717 g, 95%, mp: 132°C) as a pale grey solid. HRMS: calcd for C9HnN02 165.0790 Found, 165.0789. LRMS (El): 165 (M+ , 71 %), 108 ([NH2C6H40]+, 100). 20 1H NMR (400 MHz, CDCI3) δ 2.13 (s, 3H) 3.78 (s, 3H) 6.83 (d, 2H, 9 Hz) 7.38 (d, 2H, 9 Hz). 13C NMR (100 MHz, CDCI3) δ 24.66, 55.85, 1 14.49, 122.37, 131 .41 , 156.82, 168.79. |
| 95% |
In dichloromethane for 2h; |
4.1.1. N-(4-Methoxyphenyl)acetamide (1)
To a stirred suspension of p-anisidine (6.04 g, 49 mmol) in dichloromethane(20 mL), acetic anhydride (5 mL, 53 mmol) was addedover 1 h. The reaction was stirred for 1 h more then poured into hexane(60 mL) and stirred for 1 h. The pale grey crystals were filtered, washedwith hexane and dried; Yield 7.72 g (95%); mp 128-130 °C as reported[29]. |
| 95% |
With pentafluoroanilinium trifluoromethanesulfonate In neat (no solvent) at 20℃; for 0.25h; |
|
| 95% |
In dichloromethane for 2h; |
A.1.1 1. Preparation of the compounds Route 1: Preparation of the 5-acetamido chalcone derivatives have been done by the Claisen- Schmidt condensation of substituted benzaldehydes and 2-hydroxy-5-acetamidoacetophenone (2) has drawn below
To a stirring suspension of p-anisidine (6.036 g, 49 mmol) in DCM (20 mL), acetic anhydride (5 mL, 53 mmol) was added dropwise over a period of 1 h. The reaction was stirred for 1 h, then poured into hexane (60 mL) and stirred for further 1 h. The solid formed was collected by filtration and washed with hexane to afford the title compound 1 (7.717 g, 95%, mp: 132°C) as a pale grey solid. HRMS: calcd for C9H11NO2165.0790 Found, 165.0789. LRMS (EI): 165 (M+·, 71%), 108 ([NH2C6H4O]+, 100).1H NMR (400 MHz, CDCl3) δ 2.13 (s, 3H) 3.78 (s, 3H) 6.83 (d, 2H, 9 Hz) 7.38 (d, 2H, 9 Hz).13C NMR (100 MHz, CDCl3) δ 24.66, 55.85, 114.49, 122.37, 131.41, 156.82, 168.79. |
| 95% |
In dichloromethane for 2h; |
A.1.1 1. Preparation of the compounds Route 1: Preparation of the 5-acetamido chalcone derivatives have been done by the Claisen- Schmidt condensation of substituted benzaldehydes and 2-hydroxy-5-acetamidoacetophenone (2) has drawn below
To a stirring suspension of p-anisidine (6.036 g, 49 mmol) in DCM (20 mL), acetic anhydride (5 mL, 53 mmol) was added dropwise over a period of 1 h. The reaction was stirred for 1 h, then poured into hexane (60 mL) and stirred for further 1 h. The solid formed was collected by filtration and washed with hexane to afford the title compound 1 (7.717 g, 95%, mp: 132°C) as a pale grey solid. HRMS: calcd for C9H11NO2165.0790 Found, 165.0789. LRMS (EI): 165 (M+·, 71%), 108 ([NH2C6H4O]+, 100).1H NMR (400 MHz, CDCl3) δ 2.13 (s, 3H) 3.78 (s, 3H) 6.83 (d, 2H, 9 Hz) 7.38 (d, 2H, 9 Hz).13C NMR (100 MHz, CDCl3) δ 24.66, 55.85, 114.49, 122.37, 131.41, 156.82, 168.79. |
| 94% |
In neat (no solvent) at 20℃; for 0.0833333h; Green chemistry; |
|
| 94% |
With Co3O4 nanoparticles at 20℃; for 0.0833333h; Green chemistry; |
General procedure for acetylation of amines
General procedure: In a round-bottomed flask (25 mL) equipped with a magnetic stirrer, a mixture of aniline (0.093 g, 1 mmol) and Co3O4 (0.006 g) was prepared. Acetic anhydride (0.102, 1 mmol) was then added to the reaction mixture and stirring was continued at room temperature for 3 min. The progress of the reaction was followed by TLC. After the reaction completion, the products was extracted with EtOAc and filtered to remove Co3O4. The organic solvent was then washed with H2O (2 x 10 mL) and saturated NaHCO3 solution and then dried over anhydrous Na2SO4. The solvent was removed under vacuum to afford the pure product. |
| 93% |
With polystyrene-nanoencapsulated FeCl3 catalyst In acetonitrile at 20℃; for 0.333333h; |
2.3. A typical experimental procedure for the acetylation of alcohols, phenols, amines, and thiols with Ac 2 O catalyzed by PS-NC/ FeCl 3
General procedure: In a single-round bottomed flask (25 mL) containing a mixture of alcohol or phenol (1 mmol) and acetic anhydride (2 mmol) in CH 3 CN (4 mL) was added PS-NC/FeCl 3 (60 mg, 3.55 mol%, with respect to iron(III) content and the resulting heterogeneous mix- ture was stirred at room temperature for the time indicated in the Table ( 2 ). Upon completion of the reaction as monitored by TLC, the reaction mixture was filtered and the nanocapsules rinsed with CH 3 CN and methanol. The filtrate was washed with distilled water after quenching with a saturated solution of NaHCO 3 , dried over anhydrous MgSO 4 , and concentrated under reduced pressure us- ing a rotary evaporator to obtain the almost pure acetate products. It should be pointed out that the filtrate was analyzed at each run by ICP and atomic absorption spectroscopy to determine the leach- ing of the Fe(III) component. All products were characterized by a comparison of their spectral data (IR and 1 HNMR) and compared with the literature data. Nanoencapsulated catalyst recovery / reuse experiment, and determination of Fe in PS-NC / FeCl 3 by ICP analysis are given in ESI. |
| 92% |
With silica-supported phosphomolybdic acid at 20℃; for 0.2h; |
|
| 92% |
With ZnCl2/SiO2 In acetonitrile at 80℃; for 2.5h; |
|
| 92% |
With anhydrous Sodium acetate; glacial acetic acid |
5.1.1. N-(4-Methoxyphenyl)acetamide (9)
4-Methoxyaniline (50 g, 0.406 mol) was dissolved in a solution of sodium acetate (10.24 g, 0.125 mol) in glacial acetic acid (41 ml, 0.716 mol), the mixture was then cooled to 0 °C and acetic anhydride (45.05 ml, 0.477 mol) was added dropwise. At the end of the reaction, water (100 ml) was added to the mixture. The resulting precipitate was collected by filtration. The product was then crystallized in boiling water. The final precipitate was collected by filtration, washed with water and dried (61.70 g, 92%): mp: 126-127 °C; IR (KBr) ν: 3068 (C-H aromatic), 2934 (C-H aliphatic), 1647 (CO), 1245 (C-O) cm-1; 1H NMR (DMSO-d6, 500 MHz): δ: 2.00 (s, 3H, -NHCOCH3), 3.75 (s, 3H, -OCH3), 6.85 (d, 2H, 3-H and 5-H), 7.47 (d, 2H, 2-H and 6-H), 9.74 (s, 1H, -NHCOCH3). Anal. (C9H11NO2) theoretical: C, 65.44; H, 6.71; N, 8.48. Found: C, 65.68; H, 6.82; N, 8.32. |
| 92% |
In dichloromethane at 20℃; for 2h; |
|
| 92% |
With anhydrous Sodium acetate In glacial acetic acid at 0℃; for 0.5h; |
14 N-(4-methoxyphenyl)acetamide
To the solution of sodium acetate (10.24 g) in acetic acid (41 mL) was added 4-methoxyaniline (50 g) and the reaction mixture was cooled at 0°C. Then acetic anhydride (45.05 mL) was added dropwise under stirring. After 30 min, the reaction mixture was supplemented under stirring with water (100 mL) and the crystalline precipitate of the title compound was collected by filtration. The product was crystallized in hot water and, after cooling, collected by filtration, washed with water and dried (yield: 92%): melting point: 126-127 °C. |
| 92% |
With anhydrous Sodium acetate; glacial acetic acid at 0℃; for 0.5h; |
19
To the solution of sodium acetate (10.24 g) in acetic acid (41 ml_) was added 4- methoxyaniline (50 g) and the reaction mixture was cooled at 0°C. Then acetic anhydride (45.05 ml_) was added dropwise under stirring. After 30 min, the reaction mixture was supplemented under stirring with water (100 ml_) and the crystalline precipitate of the title compound was collected by filtration. The product was crystallized in hot water and, after cooling, collected by filtration, washed with water and dried (yield: 92%): melting point: 126-127 °C |
| 91% |
In dichloromethane |
1; 5
Para-anisidine was acylated at the amino center with acetic anhydride in dichloromethane and the product was obtained in 91% yield.; p-Anisidine was acylated at the amino center with acetic anhydride in dichloromethane, and the acylated product was obtained in 91% yield. |
| 91% |
In dichloromethane |
1; 5
1. Para-anisidine was acylated at the amino center with acetic anhydride in dichloromethane and the product was obtained in 91 % yield. Then, Friedel Craft's acyla- tion was carried out to get the hydroxyl acetophenone with acetyl chloride in the presence of anhydrous aluminium chloride in dichloromethane to give the product in 70% yield. Nitration of acetanilide derivative was carried out with nitric acid in aqueous acetic acid to get the product in 45% yield. Acetyl group of acetamido functionality was removed by refluxing in dilute hydrochloric acid for 2.5 h to get the aniline derivative in quantitative yield. Deamination was done by diazotization and treating the diazonium salt with ethanol to get the 3-nitro-2-hydroxyacetophenone. The nitro group was reduced by heating the reaction mixture in ethyl acetate with tin in hydrochloric acid resulting in the formation of corresponding amino compound. Lastly, Sandemeyer reaction was carried out to get the desired bromo derivative Va in 25% yield.; 5. p-Anisidine is acylated at the amino center with acetic anhydride in di- chloromethane and the acylated product was obtained in 91 % yield . Then, Friedel Craft's acylation was carried out to get the hydroxyacetophenone derivative with acetyl chloride in the presence of anhydrous aluminium chloride in DCM. The intermediate was isolated in 70% yield. δ-Acetamido^-hydroxyacetophenone was hydrolyzed in 2N hydrochloric solution by refluxing for 6 h, yielding 94% of δ-amino^-hydroxyacetophenone. |
| 91% |
With [Ch-OSO3H]3W12PO40 at 20℃; for 0.616667h; |
4 Example 4:
10 mmol of p-methoxyaniline,20 mmol of acetic anhydride and 0.4 mmol of heterogeneous catalyst were added to a 50 ml single-necked flask with a stir bar.Stirring was carried out at atmospheric pressure and room temperature,The progress of the reaction was monitored by thin-layer chromatography (n-hexane: ethyl acetate = 4: 1 as a developing solvent). 37min after the antiShould be the end of the filter, the filter residue with 5ml ethanol washing 3 times, collecting the filtrate to detect high-performance liquid chromatography on the AThe conversion of oxanilide was 91% and the selectivity was 100%. The yield of N-acetyl-p-methoxyaniline was calculated.The rate was 91%. The washed residue was vacuum dried at 120 ° C and then recycled. |
| 91% |
With copper(II) tetrafluoroborate hexahydrate at 20℃; for 1h; |
N-(4-Methoxyphenyl)acetamide 2d
Preparation of 2d is described as a typical procedure (method A). A mixture of p-anisidine (861 mg, 7 mmol), Cu(BF4)2*6H2O (24 mg, 0.07 mmol), and acetic anhydride (7 mL) was stirred at rt for 1 h, then poured into saturated aqueous NaHCO3 at 0°C and extracted with 10% CH3OH-CH2Cl2 (100 mL×2). The organic layer was washed with brine, dried over Na2SO4, and evaporated in vacuo. The residue was purified by chromatography [silica gel, ethyl acetate/hexane (3:2)] to give 2d (1.047 g, 91%). Mp 130.0-130.5 °C, red needles (recrystallized from AcOEt-hexane). IR (KBr) (cm-1): 3282,1664. 1H NMR (300 MHz, CDCl3) δ 7.39 (2H, d, J= 8.9 Hz), 7.14 (1H, br-s, NH), 6.86 (2H, d, J=8.9 Hz), 3.79 (3H, s, OCH3), 2.15 (3H, s, Ac). MS (EI) m/z: 165 (M+,83), 108 (100), 43 (8). HRMS (EI) m/z: Calcd for C9H11NO2: 165.0790, found 165.0788. |
| 90% |
In dichloromethane |
|
| 89% |
With triethylamine In dichloromethane |
|
| 89% |
With anhydrous Sodium acetate In toluene for 1h; Reflux; |
p-methoxy-acetanilide (5)
The p-anisidine (4, 1 mM) was acylated with acetic anhydride (2 mM) in the presence of sodium acetate as a base, by heating under reflux in toluene for about 1 hr. After the completion of the reaction (monitored using TLC), the toluene was removed under reduced pressure to yield the acylated product for the use in the next reaction. % yield = 89%; mp. 131°C;1H-NMR(300MHz, DMSO-d6): δ 2.14 (s, 3H), 3.89 (s, 3H), 6.86 (d, 2H,J= 8.73Hz), 7.45 (d, 2H,J= 8.43Hz), 9.81 (s, 1H);IR(KBr, cm-1): 2931, 2362, 1725, 1618, 1209, 769;MS: m/z 166.5 (M+1)+. |
| 89% |
In lithium hydroxide monohydrate at 50℃; for 0.1h; |
A general procedure for acetylation of arylamines with Ac2O/F3O4/Cu MNPs system
General procedure: In a round-bottom flask (10 mL) equipped with a magnetic stirrer, a mixture of PhNH2(1 mmol, 0.093 g) and H2O(3 mL) in oil bath (50 °C) was prepared. Magnetically recyclable nanoparticles of Fe3O4/Cu (0.05 mmol) was then added, and the mixture was stirred for 1 min under oil bath conditions. Addition of Ac2O(1 mmol, 0.102 g) to the prepared mixture was followed by stirring for 3 min at 50 °C. After completion of the reaction, the copper nanocatalyst was separated by an external magnet and the mixture was extracted with EtOAc (3 × 8 mL). Organic layers were then dried over anhydrous sodium sulfate. Evaporation of the solvent under reduced pressure affords the pure acetanilide in 95% yield (0.128 g, Table 2, entry 1). |
| 89% |
In neat (no solvent) at 20℃; for 0.25h; Sonication; Green chemistry; |
Typical experimental procedure forN-acylation of amines and sulfonamides
General procedure: In a glass tube was placed a mixture of amine or sulfonamide derivatives (1 equiv) and acetic anhydride (1equiv) at room temperature. The mixture was immersed in the water of the sonicator bath for appropriate time at room temperature. Reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with the water, and extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate and the resulting residue was purifed by silica gel chromatography using dichloromethane-petroleum ether (9:1), to give the N-acylamines or N-acylsulfonamides in good yieds. |
| 88% |
With sodium lauryl sulfate In lithium hydroxide monohydrate |
|
| 87.3% |
In dichloromethane at 20℃; for 6h; |
2 4.1.2 N-(4-methoxyphenyl)acetamide (2)
p-Methoxyaniline (12.3 g, 0.1 mol) was dissolved in 120 mL of CH2Cl2. Acetic anhydride (10.2 g, 9.44 mL, 0.1 mol) was added dropwise to this solution in an ice/water bath for 6 h at room temperature. The reaction mixture was quenched and filtered by petroleum ether. The product is white power (14.4 g, 87.3% yield). m.p. 127-129 °C. |
| 85% |
With glacial acetic acid at 110℃; for 2h; |
|
| 85% |
In neat (no solvent) at 20℃; for 0.2h; Green chemistry; |
Typical experimental procedure for thesynthesis of N-Acylated amines, amino alcohols and sulfonamides
In a 50mL round-bottomed flask, a mixtureof amine or amino alcohol (1 mmol) and aceticanhydride (1.2 mmol) was stirred at roomtemperature for the appropriate time. Aftercompletion of the reaction, as monitored by TLC,the reaction mixture was dissolved in ether (5 mL)and was allowed to stand at room temperature for1 hour. During this time, crystal of product formed,which were collected by filtration.In the case of solid substrates(sulfonamides), the same protocol was used.However, the use of water was required for thesolubility of the mixture. The N-acylatedsulfonamides were collected by crystallization fromdiethyl ether. |
| 85% |
With triethylamine In dichloromethane at 20℃; |
|
| 84% |
In dichloromethane at 20℃; Inert atmosphere; |
|
| 84% |
In dichloromethane at 20℃; Inert atmosphere; |
|
| 80% |
With pyridine; aluminum(III) oxide at 130 - 132℃; for 2h; microwave irradiation; |
|
| 77% |
With pyridine |
|
| 76% |
for 0.00277778h; Green chemistry; |
General procedure for the synthesis of acetamides 3a-p,5a-d, and 7
General procedure: To a 10 mL round bottom flask was added 0.5 mmolof the amine and 0.1 mL of acetic anhydride. The reactionis instantaneous and exothermic, and after 10 s the solidproduct formed was filtered and washed with cold water.When no solid was immediately formed, 4 mL of coldwater was added, and the mixture allowed standing ina refrigerator for 24 h, leading to precipitation. To allsynthesized acetamides, measured physical data were inagreement to the reported values.17-19,27,31,32 |
|
With sodium hydroxide |
|
|
With pyridine for 2h; Heating; |
|
|
With glacial acetic acid Heating; |
|
|
In glacial acetic acid for 0.25h; Heating; |
|
|
In lithium hydroxide monohydrate |
|
|
With glacial acetic acid In lithium hydroxide monohydrate at 30 - 50℃; for 2 - 3h; |
Examples; 4-methoxy acetanilide:
p-anisidine (10 GM), Acetic anhydide (12 gm.) & acetic acid (20 ml) are added in WATER (50 ML. ) AT 30-35°C. THE REACTION MIXTURE IS HEATED TO 45-50°C FOR 2-3 HOURS. The reaction mass is cooled. Water (50 ml.) is added to reaction mass with stirring & filtered to get 4-methoxy acetanilide. The yield of the product is 11 gm |
| 164 mg |
In tetrahydrofuran; lithium hydroxide monohydrate for 0.5h; |
|
|
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; |
|
|
With pyridine at 0 - 20℃; |
|
|
With 4-dimethylaminopyridine In dichloromethane |
|
|
With pyridine at 0 - 20℃; for 0.666667h; Inert atmosphere; |
|
|
In dichloromethane |
|
|
In dichloromethane at 20℃; Inert atmosphere; |
Representative procedure for the preparation of N-aryl amides:
General procedure: To a round-bottom flask were added 3-methoxyaniline (1.4 mL, 12.2 mmol, 1.0 equiv.), acetic anhydride (1.4 mL, 14.6 mmol, 1.2 equiv.) and dry DCM (35 mL). The reaction was stirred at room temperature and monitored by TLC. Then the reaction mixture was washed with a saturated solution of sodium carbonate, the organic layers were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by flash chromatography with petroleum ether/ ethyl acetate or recrystallization. The yields of the N-aryl amides are ranging from 60% to 98% and all the substrates N-aryl amides are known compounds. |
|
With glacial acetic acid Reflux; |
|
|
In dichloromethane at 20℃; |
|
|
at 20℃; for 0.5h; |
|
|
With platinum nanoparticles supported on zirconia In methanol at 20℃; for 0.5h; |
|
|
With glacial acetic acid |
|
|
With triethylamine In dichloromethane |
|
|
With 4-dimethylaminopyridine In dichloromethane at 0 - 20℃; Inert atmosphere; |
|
|
In dichloromethane at 20℃; Inert atmosphere; |
|
|
In dichloromethane at 20℃; for 1h; |
|
|
With glacial acetic acid |
|
|
With dodecanesulphonic acid sodium salt In lithium hydroxide monohydrate at 20℃; for 0.5h; |
|
|
With glacial acetic acid Reflux; |
|
|
With glacial acetic acid |
|
|
With hydrogenchloride; potassium carbonate In lithium hydroxide monohydrate |
|
|
In dichloromethane at 20℃; Inert atmosphere; |
|
| 76 %Chromat. |
With Magnetically separable γ-Fe2O3 nanoparticles In neat (no solvent) at 28℃; for 1h; Sealed tube; Sonication; |
2.4. General procedure for acylation reaction
General procedure: A 25mL sealed tube containing a magnetic stir bar was charged with phenol/alcohol/amine (1mmol) and acetic anhydride (1.5mmol), nano γ-Fe2O3 (5mol%, 8mg) as catalyst. The reaction mixture was kept for sonication in sonication bath at room temperature (28°C) for 1h. The ultrasonic bath (Labman Scientific Instruments, Model - LMUC 4) had a frequency of 33kHz and electric power rating of 100W. The reaction progress was monitored on thin-layer chromatography (TLC) and gas chromatography (PerkinElmer, GC Clarus 400) analysis. After completion of the reaction, the reaction mixture was diluted with ethyl acetate and catalyst was separated from reaction mixture by using a strong magnet. The separated catalyst was washed with distilled water and absolute ethanol several times then dried in oven and reused for further reaction. The reaction mixture was washed with saturated NaHCO3 solution (1×15mL) and the product was extracted with ethyl acetate (3×10mL) and dried over Na2SO4 and evaporated under vacuum. All the obtained products are well known in the literature and were confirmed by gas chromatography-mass spectrometry (Shimadzu GCMS-QP 2010) analysis by comparison with literature data. |
|
With triethylamine In dichloromethane at 0 - 20℃; |
|
|
With glacial acetic acid for 0.5h; Heating; |
|
|
at 0 - 25℃; |
|
|
Reflux; |
|
|
In dichloromethane at 20℃; Inert atmosphere; |
Anilides 1;17 General Procedure
General procedure: Arylamine (10.0 mmol; 1 equiv) was added to a round-bottom flask and fitted with a rubber septum. The flask was purged with N2 and anhyd CH2Cl2 (3 mL/1 mmol) was added. Ac2O (12.0 mmol, 1.2 equiv) was added and the reaction was stirred at r.t. and monitored by TLC. Upon completion, the reaction mixture was washed with a sat. aq Na2CO3, the organic layer was dried (MgSO4), and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography using EtOAc/n-hexane as eluent. |
|
In hexane; toluene; acetonitrile at 20℃; Inert atmosphere; |
Radical deprotection of SeES amide 4b: Typical procedure
To a solution of SeES amide 4b (170 mg, 0.500 mmol) in freshly distilled toluene (10 mL) were simultaneously added 1.00 mL of AIBN solution (330 mg, 2.00 mmol, of AIBN in 2.00 mL of acetonitrile) and 1.00 mL of tributyltin hydride solution (1161 mg, 3.99 mmol, of tin hydride in 2.00 mL of hexane) over the period of 20 h using syringe pump under nitrogen atmosphere at 80 °C. After the resulting mixture was stirred for additional 1 h at 80 °C, acetic anhydride (1 mL, 10.6mmol) was added before stirring overnight at room temperature. The volatiles were evaporated out, and the residue was chromatographed (eluent: ethyl acetate/hexane = 1/1, v/v) to obtain 53 mg (79 %) of acetanilide as the colorless crystal. |
|
With anhydrous Sodium acetate; glacial acetic acid |
|
|
In neat (no solvent) Heating; |
|
|
Reflux; |
|
|
In chloroform for 2h; Inert atmosphere; |
5
Under nitrogen protection,A mixture of p-methoxyaniline (100 mmol, 12.32 g),Acetic anhydride (llOmmol, 10.4ml)Was dissolved in 40 ml of methylene chloride and stirred for two hours. The solvent was evaporated to give the crude product in a yield of 97.6%. |
|
In dichloromethane at 30℃; for 2h; Inert atmosphere; |
4.1.1. Synthesis of N-(4-methoxyphenyl)acetamide
Acetic anhydride (16.58 g, 162.40 mmol) was slowly drippedinto a stirred solution of 4-methoxyaniline (1) (10 g, 81.20 mmol)in CH2Cl2 (120 mL) using dropping funnel. After the dripping of acetic anhydride, the reaction mixture was purged with N2 gasand stirred at 30°C for 2 h, and then the mixture was evaporated to give silver-white crude product 12.60 g (76.27 mmol, 94%). 1HNMR (300 MHz, DMSO-d6): d 9.72 (s, 1H), 7.48-7.45 (m, 2H),7.21-6.70 (m, 2H), 3.98 (s, 3H), 1.20 (s, 3H). Used directly for followingreaction without further purifying. |
|
With triethylamine In dichloromethane at 0℃; |
|
|
at 20℃; |
General procedure for the synthesisof N-(4-methoxyphenyl)acetamide (9)
p-Aanisidine (0.123 g, 1 mmol) and 0.2 cm3 acetic anhydride(2 mmol) were grinded in a mortar at roomtemperature. The grinding was continued for 30 more s,and the progress of the reaction was monitored by TLC.After the completion of the reaction, 10 cm3 water wasadded to the mixture and the product collected by filtrationand washed with additional water. |
|
With hydrogenchloride In lithium hydroxide monohydrate |
Step I Preparation of ortho substitutedacetanilide8, 9
General procedure: Aniline (5 ml) is dissolved in hydrochloricacid (4.6 ml concentrated hydrochloric acid and12.5ml water) in a beaker. To the clear solution are added acetic anhydride (6.5 ml).The mixture is stirreduntil acetic anhydride has completely reacted. Themixture are immediately poured in to a solution ofsodium acetate (8.3 gm) in water (25 ml).The solutionis stirred and cooled in ice. The separated acetanilideis fltered. It is recrystallized from boiling water(100-125 ml) to which ethyl alcohol has been added(Table 1). |
|
With glacial acetic acid In lithium hydroxide monohydrate at 0 - 95℃; |
|
|
at 0 - 25℃; |
|
|
for 2h; Reflux; Green chemistry; |
2.1
(1) In 1500g of p-methoxyaniline, 1000g of acetic anhydride was added and the mixture was refluxed for 2 hours. |
|
for 0.5h; Sonication; |
1 Example 1
P-methoxyaniline (24.6 g, 0.2 mol) was placed in a 500 mL beaker, and 30 mL of acetic anhydride (molar ratio 1:2) was quickly added, stirred vigorously, and ultrasonicated for half an hour.At this time, the material was viscous, and a small amount of plate (petroleum ether: ethyl acetate = 1:1) was completely reacted, and 100 mL of water was added, and the crystal was allowed to stand for 2 hours, and the precipitated solid was filtered off.The filter cake was washed with water and dried to give an off-white solid p-methoxyacetanilide. |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
