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CAS No. : | 103-89-9 | MDL No. : | MFCD00008677 |
Formula : | C9H11NO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | YICAMJWHIUMFDI-UHFFFAOYSA-N |
M.W : | 149.19 | Pubchem ID : | 7684 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.22 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 45.72 |
TPSA : | 29.1 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.0 cm/s |
Log Po/w (iLOGP) : | 1.79 |
Log Po/w (XLOGP3) : | 1.7 |
Log Po/w (WLOGP) : | 1.76 |
Log Po/w (MLOGP) : | 1.84 |
Log Po/w (SILICOS-IT) : | 1.84 |
Consensus Log Po/w : | 1.79 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.11 |
Solubility : | 1.16 mg/ml ; 0.00781 mol/l |
Class : | Soluble |
Log S (Ali) : | -1.93 |
Solubility : | 1.77 mg/ml ; 0.0118 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -3.15 |
Solubility : | 0.105 mg/ml ; 0.000705 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | at 90℃; for 10 h; Cooling with ice | 2) 3.5 ml of DMF and 17 ml of POCl3 were mixed under ice-cooling,After stirring, 2.24 g (15 mmol) of compound 1 was added, and the resulting solution was placed in a reflux apparatus,Heated to 90 ° C for 10 hours, cooled and poured into 500 ml of ice water, and the compound 2(2.7 g, yield 87percent). |
87% | at 90℃; for 10 h; Cooling with ice | 2) 3.5 ml DMF and 17 ml POCl3 are mixed under ice bath, then add 2.24g (15mmol) compound 1, the resulting solution is placed in reflux device, heating to 90 °C reflux for 10 hours, after cooling is poured into 500 ml ice water, filtered to obtain compound 2 (2.7g, yield 87percent). |
84.83% | With bis(trichloromethyl) carbonate In chloroform at -5 - 51℃; for 6.5 h; Green chemistry | This example provides a process for the synthesis of 2-chloro-3-formyl-6-methylquinoline with the following main steps: under ice-salt bath, 3.00g (20.13 mmol) acetanilide, 8.03 g (27.04 mmol) of BTC and 10 mL of trichloromethane 4.2 mL (54.66mmol) DMF was added dropwise over 80 min after the temperature was maintained below -5 °C. The rate of the bubble overflow was controlled by the tail gas uptake rate. After the addition of the DMF, the mixture was stirred continuously for 10 min. For water bath, plus Heat to 51 °C, reaction 5 hours, steaming part of the solvent, adding ice water, 10percent NaOH to adjust the pH to 8 ~ 9, pumping, recrystallization. The yield was 84.83percent. |
77% | at 0 - 65℃; for 8 h; | General procedure: At 0 °C to a stirred solution of POCl3 (39.6 g, 259 mmol) and anhydrous DMF (8 g, 111mmol) was added acetanilide (5 g, 37 mmol). The mixture was then heated to 65 °C and the progress of the reaction was monitored by TLC analysis. After 8 h the reaction mixturewas then cooled to room temperature and added cautiously into ice-cold water. The solid precipitated was collected by filtration to isolate the compound 1a as yellow solid. |
66.7% | at 0 - 85℃; | POCl3 (111 mL, 1.19 mol) was added drop wise to DMF (40 mL, 0.51 mol) at 0 °C, followed by a portion wise addition of N-acetyl-p-toluidine (S2) (25.7 g, 0.17 mol). The resulting mixture was stirred for 30 min at rt and the reaction mixture heated at 85 °C for 6 h. The resulting solution was cooled to rt and slowly poured into ice-water. The resulting precipitate was filtered, washed with water, dried and crystallized from ethyl acetate to give aldehyde (S3) (23.6 g, 66.7percent). 1H NMR (400 MHz, DMSO-d6 ppm): 2.48 (s, 3H), 7.79 (d, 1H), 7.91 (d, 1H), 8.01 (s, 1H), 8.81 (s, 1H), 10.35 (s, 1H). m/z (APCI+) 206 (M+H+). mp 124-125 °C. |
64% | Stage #1: at 0℃; for 0.25 h; Stage #2: for 4 h; Reflux |
General procedure: Dimethylformamide (12 mmol, 3 equiv.) was cooled at 0°C in a round flask equipped with a drying tube and phosphorus pentachloride (18 mmol, 4.5 equiv.) was added slowly and the mixture was stirred for 15 minutes keeping the temperature below 0°C. To this solution was added in a portion the corresponding acetanilide (4 mmol, 1 equiv.) and the reaction mixture was heated under reflux and stirring for the appropiate time depending of the acetanilide. The resulted mixture was cooled to 0°C and the solution was poured slowly into ice-water and stirring for ten minutes, obtaining a yellow solid which was filtered, washed several time with cold water and dried under vacuum. The 2-chloroquinoline-3-carbaldehydes were recrystallized according to the literature. |
34% | Stage #1: at 0℃; Heating / reflux Stage #2: at 0℃; |
Step 2: 2-Chloro-6-methylquinoline-3-carbaldehyde Phosphoryl trichloride (237.2 g, 1.55 mol) was added dropwise with stirring, while cooling to 0° C. to N,N-dimethylformamide (40.4 g, 552.74 mmol). N-p-Tolylacetamide (33 g, 221.19 mmol) was then added and the resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at reflux. The reaction mixture was then quenched by the adding 3000 ml of H2O/ice. Adjustment of the pH to 9 was accomplished by the addition of Na2CO3. The resulting solution was extracted with DCM (3*3000 mL). The organics were combined, dried over MgSO4, and concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by column chromatography on silica gel eluding with a 1:10 EtOAc:hexanes to afford 15.3 g (34percent) of 2-chloro-6-methylquinoline-3-carbaldehyde as a yellow solid. LCMS: 206 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | for 10 h; Reflux | General procedure: To the prepared TCTA–DMFreagent, 9.8 mmol of the Acetanilide was added and stirred under refluxconditions. Progress of the reaction was checked by TLC till the completion ofthe reaction. Analytical TLC was carried out using Merck aluminum-backed0.2 mm silica gel 60 F-254 plates. Column chromatography was conductedusing Merck silica gel 60 (230–400 mesh). After completion of the reaction,water was added to the reaction mixture and stirred for a few more minutes toextract inorganic components into water. The organic layer was separated andthe crude product thus obtained was further purified with columnchromatography (silica gel, ethyl acetate/n-hexane) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | With Selectfluor; sodium chloride In water for 24 h; Reflux | 1a as example: To a stirred suspension of N-(p-tolyl)acetamide 1a (75 mg, 0.5 mmol) and Selectfluor (213 mg, 0.6 mmol) in water (3.0 mL) was added HBr (40percent aqueous, 0.08 mL, 0.55 mmol), and the mixture was stirred for 5 min at room temperature. After 1a was consumed, as indicated by TLC, the reaction mixture was quenched with saturated aqueous Na2S2O3 (2.0 mL) and water (20.0 mL), and extracted with CH2Cl2 (10.0 mL) three times. The residue obtained after evaporation of the solvent was purified by column chromatography on silica gel (petroleum ether–ethyl acetate = 6:1, v/v) to afford N-(2-bromo-4-methylphenyl)acetamide 2a as a white solid (108 mg, 95percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In dichloromethane at 20℃; Inert atmosphere; | |
99% | With Methylenediphosphonic acid at 20℃; for 1h; neat (no solvent); | |
98% | With pyridine; aluminum(III) oxide at 125 - 127℃; for 2h; microwave irradiation; |
98% | With lanthanum(III) nitrate at 20℃; for 0.25h; | |
98% | With cadmium(II) oxide at 80℃; for 0.166667h; Neat (no solvent); Microwave irradiation; | |
98% | With mesoporous silica for 0.025h; Microwave irradiation; neat (no solvent); | |
98% | With tris(pentafluorophenyl)borate In neat (no solvent) at 20℃; for 0.0166667h; Green chemistry; | Typical experimental procedure: General procedure: B(C6F5)3 (0.5 mol %) was added to a mixture of alcohol/phenol/thiophenol/amine (1 mmol) and acetic anhydride (1.2 mmol), and the reaction mixture was stirred at room temperature until the complete conversion of starting material (monitored by TLC). After completion of reaction, the reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (3 15 mL). The organic layer was washed with cold saturated sodium bicarbonate solution (2 20 mL) followed by brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure and products were purified over silica gel column chromatography in ethylacetate/hexane. All compounds were characterized and confirmed by comparison of their spectral data and physical properties with reported literature. |
98% | With triethylamine In dichloromethane at 20℃; Inert atmosphere; | |
97% | In neat (no solvent) at 20℃; for 0.5h; | |
97% | at 20℃; for 4h; | |
97% | at 0 - 20℃; Inert atmosphere; | |
97% | With Ni2B-Cu2O nanocomposite In neat (no solvent) at 40℃; for 0.0333333h; | General procedure for the direct N-acetylation of arylamines using solvent-free mechanochemical grinding General procedure: For example, a mixture of aniline (1 mmol), Ni2B-Cu2O (54 mg), and acetic anhydride (1 mmol) was ground using a simple porcelain mortar and pestle for a minute at 40 C (in an oil bath). Reaction progress was monitored by TLC with nhexane:EtOAc:MeOH (5:3:1) as eluent. After reaction completion, the reaction mixture was cooled to room temperature, then 5 mL distilled water was added to the reaction vessel; subsequently, the reaction mixture was transferred to a flask (25 mL) equipped with a magnetic stirrer. The mentioned mixture was stirred vigorously for 2 min. Next, the product was extracted with dichloromethane (5 9 3 mL). Extraction solution was dried with anhydrous sodium sulfate then passed through a cotton filter. Evaporation of the solvent afforded pure acetanilide in 98 % yield. |
97% | With glacial acetic acid at 20℃; for 0.5h; | |
96% | With ZnAl2O4 nanoparticles at 20℃; for 0.05h; Neat (no solvent); | |
96% | With pentaaminechlorocobalt(III) dichloride; phosphoric acid In neat (no solvent) at 75℃; for 0.166667h; Green chemistry; chemoselective reaction; | |
96% | With silica-coated ferrite nanoparticles supported with montmorillonite-K10 at 20℃; for 0.166667h; | |
95% | With silica-bonded N-propyl sulfamic acid at 20℃; for 0.166667h; chemoselective reaction; | |
95% | With nickel zirconium phosphate In neat (no solvent) at 40℃; for 0.166667h; | General experimental procedure for the acetylation of substrates under solvent-free conditions General procedure: ZPNi (1 mol %) was added to a mixture of alcohol(1 mmol) and AA (2 mmol), and the resulting mixture was stirred at 40 °C for the specified time (Scheme 2). Upon completion of the reaction (as determined by GC), the catalyst was separated from the reaction mixture by centrifuge,then the supernatant was collected and diluted with 10 %NaHCO3 solution (10 ml) before being extracted with Et2O(2 × 10 ml). The combined organic extracts were washed and then dried over anhydrous CaCl2 before being evaporated to dryness under vacuum to give the desired product. In some cases, it was necessary for the product to be purified by column chromatography over silica gel eluting witha mixture of cyclohexane and ethyl acetate. |
94% | at 20℃; | |
94% | at 20℃; for 0.25h; | |
94% | With 1,8-diazabicyclo[5.4.0]undec-7-en-8-ium acetate In neat (no solvent) at 50℃; for 0.5h; Green chemistry; | |
94% | 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. |
94% | With Co3O4 nanoparticles at 20℃; for 0.05h; 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. |
93.7% | In acetonitrile for 1h; Heating; | |
93% | In chloroform for 96h; | |
93% | With Mg-Al hydrotalcite with Mg/Al molar ratio in 2-3.5 In lithium hydroxide monohydrate at 20℃; for 0.0833333h; | |
93% | With anhydrous Sodium acetate In lithium hydroxide monohydrate for 0.166667h; Heating; | |
92% | With melamine trisulfonic acid In dichloromethane at 20℃; for 0.05h; | |
92% | With [Ch-OSO3H]3W12PO40 at 20℃; for 0.45h; | 3 Example 3: 10 mmol of p-methylaniline, 15 mmol of acetic anhydride and 0.3 mmol of heterogeneous catalystAgent was 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). 27min 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 yield of N-acetyl-p-methylaniline was calculated as 92% of the conversion of the aniline and 100% of the selectivity92%. The washed residue was vacuum dried at 120 ° C and then recycled. |
91% | In lithium hydroxide monohydrate at 50℃; for 0.05h; | 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). |
91% | With pyridine | |
90% | With saccharin sulfonic acid In dichloromethane at 20℃; for 1h; | |
90% | With poly(4-vinylpyridine) supported copper(II) oxide nanoparticles In neat (no solvent) at 20℃; for 0.166667h; chemoselective reaction; | General procedure for the acetyl protection reactions General procedure: A mixture of the substrate (1 mmol), acetic anhydride(1 mmol) and PC-NPs (12 mg) was stirred at room temperature. After completion of the reaction (monitored by TLC using a 1:1 mixture of EtOAc/n-hexane), EtOAc (15 mL)was added and the catalyst was filtered. The organic layer was washed with saturated solution of NaHCO3 and water(3 × 15 mL), and dried over anhydrous MgSO4. Evaporation of the solvent under reduced pressure gave the requested acetates in high purity. |
90% | Stage #1: <i>p</i>-toluidine With anhydrous sodium carbonate In dichloromethane at 0℃; Stage #2: acetic anhydride at 20℃; for 3h; | Synthesis of N-(4-methylphenyl)acetamide To a solution of 4-methylaniline (5.30 g, 49.46 mmol) indichloromethane (100 mL) was added anhydrous Na2CO3(5.24 g, 49.46 mmol) under stirring at 0°C. And then aceticanhydride (7.57 g, 74.19 mmol) was added dropwise. Afteraddition, the resulting mixture was stirred for 3 h at roomtemperature. TLC monitoring indicated that starting materials consumed completely. After fltration and washing solidwith acetone, the solid was recrystallized from dichloromethaneto aord colorless crystals 6.64 g (90%). M.p.: 153-154°C(CH2Cl2) (Lit.35 154°C).1H NMR (400 MHz, CDCl3): δ = 2.13(s, 3H, CH3), 2.30 (s, 3H, CH3), 7.09 (d, J = 8.2 Hz, 2H, ArH),7.37 (d, J = 8.3 Hz, 2H, ArH), 7.60 (br, 1H, NH). |
90% | With polydopamine sulfamic acid-functionalized silica gel nanocatalyst In neat (no solvent) at 20℃; for 2h; | 2.2 General Procedure for Acylation Reaction General procedure: A 25 mL ballon containing a magnetic stir bar was chargedwith phenol/alcohol/amine (1 mmol) and acetic anhydride(2 mmol), SiO2/PDA-SO3H (30 mg, 1 mol% H+)as catalyst.The reaction mixture was stirred at room temperature and thereaction progress was monitored on thin-layer chromatography(TLC). After completion of the reaction, the reaction mixturewas diluted with ethyl acetate and catalyst was separatedfrom reaction mixture by centrifugation. The reaction mixturewas washed with sat. NaHCO3solution (1 × 15 mL) and theproduct was extracted with ethyl acetate (3 × 10 mL) and driedover Na2SO4and evaporated under vacuum. All the obtainedproducts are well known in the literature. |
90% | With pentafluoroanilinium trifluoromethanesulfonate In neat (no solvent) at 20℃; for 0.166667h; | |
89% | 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. |
89% | With hydrogenchloride In lithium hydroxide monohydrate for 4h; Cooling with ice; | 1 1) 10.7 g (0.1 mol) of p-toluidine, 50 ml of water was added to a 250 ml round bottom flask, 8 ml of concentrated hydrochloric acid was added dropwise,10.2 g (0.1 mol) of acetic anhydride, reacted under ice bath for 4 hours, and then adjusted to pH 7 with 20 w / w% sodium acetate solution. The pH was adjusted to 7, and the filter cake was recrystallized from absolute ethanol to give the compound 1 (white needle-like crystals,13.3 g, yield 89%). |
89% | With hydrogenchloride In lithium hydroxide monohydrate for 4h; Cooling with ice; | 1 1) 10.7g (0.1 mol) p-toluidine, 50 ml water were added to the 250 ml round-bottom flask. Add dropwise 8 ml concentrated hydrochloric acid, 10.2g (0.1 mol) acetic anhydride. The reaction under ice bath for 4 hours, then use 20 w/w % of sodium acetate solution of the system is adjusted pH value is 7, standing, filtering, the filter cake is anhydrous ethanol recrystallization to obtain compound 1 (white needle crystal, 13.3g, yield 89%). |
88% | In benzene at 100℃; for 0.5h; | 13 4.1.13 N-(p-Tolyl)acetamide (19) p-Toluidine (32.2 g, 0.3 mol) was dissolved in benzene (60 mL). To this solution was added acetic anhydride (31 g, 0.3 mol) dropwise at 100 °C and stirred for 30 min. When cooled to room temperature, the resulting precipitate was filtered and washed with petroleum ether, dried to give product 19 (39.5 g, 88%) as white acicular crystal. Mp: 147-149 °C (lit. |
88% | With Fe3O4-polyethylene glycol composite magnetic nanoparticles In neat (no solvent) at 20℃; for 0.5h; Sonication; Green chemistry; | General procedure for acylation reaction under ultrasonic conditions General procedure: A 10-mL balloon was charged with phenol/alcohol/amine (1mmol) and acetic anhy-dride (3mmol), with Fe 3 O 4 PEG (10mg) as catalyst. The reaction balloon was taken in the ultrasonic bath, where the level of the reaction mixture is lower than the surface of the water. Then, the mixture was sonicated under 60W of power of the ultrasonic bath at room temperature for the appropriate time, as shown in Table2. After completion of the reaction (monitored by thin-layer chromatography), the reaction mixture was diluted with ethyl acetate and the catalyst was separated from reaction mixture by an external magnet. The separated catalyst was washed with DI water and absolute ethanol several times then dried in oven and reused for further reaction. The reaction mixture was washed with sat. NaHCO 3 solution (1 × 15mL) and the product was extracted with ethyl acetate (3 × 10mL) and dried over Na 2 SO 4 and evaporated under vacuum. All the obtained products are well known in the liter-ature and were confirmed by nuclear magnetic resonance (NMR) analysis and com -parison with literature data. |
88% | With 7% w/w Pd/C In lithium hydroxide monohydrate for 0.0833333h; Reflux; Green chemistry; | General procedure for the N-acetylation of arylamines catalyzed by Pd/C General procedure: To the synthesis of N-phenylacetamide (acetanilide) as a representative example, a mixture of aniline (1 mmol, 0.093 g) and H2O (2 mL) was prepared in around-bottom flask (15 mL), which equipped with a magnetic stirrer. Then, Pd/C(24 mg) was added into the reaction environment, and the resulting mixture was stirred at reflux. Next, Ac2O (1 mmol, 0.102 g) was added to the prepared mixture followed by stirring for 2 min at reflux. After completion of the acetylation reaction (monitored by TLC using n-hexane:EtOAc (5:1) as an eluent), the mixture was cooled to room temperature, and the Pd/C catalyst was separated by filtration. Then, the reaction mixture was extracted with DCM (3 × 5 mL) and then dried over Na2SO4. Finally, evaporation of the solvent under reduced pressure afforded the pure acetanilide in 88% yield. |
87% | With ZnCl2/SiO2 In acetonitrile at 80℃; for 3h; | |
87% | In toluene | |
84% | In neat (no solvent) at 20℃; for 0.216667h; 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. |
83% | With sodium lauryl sulfate In lithium hydroxide monohydrate | |
77% | With 4-butylazobenzyl-4′-triazologlucuronic acid sodium salt In lithium hydroxide monohydrate at 20℃; Irradiation; | |
73.4% | With triethylamine In acetonitrile at 50℃; for 3h; | 4.2.1. N-Acetyl-p-toluidine (S2) TEA (24.8 g, 0.25 mol) was added at once to a solution of 25.0 g (0.23 mol) p-toluidine in 50 mL of MeCN, followed by a dropwise addition of acetic anhydride (25.2 g, 0.25 mol). The reaction mixture was stirred for 3 h at 50 °C (TLC control). The mixture was cooled to 0 °C and the resulting precipitate was filtered, washed with water (2 × 25 mL) and dried on the air to afford N-acetyl-p-toluidine (S2) (25.7 g, 73.4%). m/z (APCI+) 150 (M+H+). Mp 145-146 °C. |
60% | With supported L-pyrrolidine-2-carboxylic acid-4-hydrogen sulfate on Silica Gel at 20℃; for 0.5h; Green chemistry; | |
With benzene | ||
With lithium hydroxide monohydrate | ||
With pyridine for 2h; Heating; | ||
With glacial acetic acid Heating; | ||
In glacial acetic acid for 0.25h; Heating; | ||
In lithium hydroxide monohydrate | ||
In glacial acetic acid at 20℃; | 1 1 mol of 1-amino-4-methylbenzene was dissolved in 150 mL of acetic acid, and acetic anhydride was dropped therein at room temperature, and then they were stirred. After the completion of the reaction, solid matter precipitated was filtered, and was then dried after washing with water. | |
In dichloromethane | ||
In dichloromethane at 20℃; | ||
at 20℃; for 0.5h; | ||
With platinum nanoparticles supported on zirconia In methanol at 20℃; for 0.5h; | ||
96 %Chromat. | With C13H16NO6S2(1+)*HO4S(1-) at 25℃; for 0.333333h; Green chemistry; | |
In dichloromethane at 20℃; Inert atmosphere; | ||
With dodecanesulphonic acid sodium salt In lithium hydroxide monohydrate at 20℃; for 0.5h; | ||
With glacial acetic acid Reflux; | ||
With hydrogenchloride; potassium carbonate In lithium hydroxide monohydrate | ||
In dichloromethane at 20℃; Inert atmosphere; | ||
With glacial acetic acid | ||
In dichloromethane at 20℃; | ||
With triethylamine In dichloromethane at 0 - 20℃; | ||
With glacial acetic acid for 0.5h; Heating; | ||
at 0 - 25℃; | ||
With pyridine for 0.0833333h; | Derivatization General procedure: For the preparation of the acetyl derivatives, each amine was treated with a mixture (1 mL) of acetic anhydride (95%) and pyridine (5%). After 5 min, the reaction mixture was acidified with 1 M HCl (0.75 mL), and extracted into dichloromethane (1 mL). The extracts were then dried with a stream of N2 to obtain the products as solids or oily residues. | |
at 20℃; for 1h; | ||
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. | |
With anhydrous Sodium acetate; glacial acetic acid | ||
Reflux; | ||
With triethylamine In dichloromethane at 20℃; for 3h; | ||
at 0 - 25℃; | ||
at 20℃; | ||
In glacial acetic acid for 1h; Reflux; | ||
In dichloromethane at 0 - 20℃; Inert atmosphere; | ||
In dichloromethane at 0℃; for 0.333333h; Inert atmosphere; Schlenk technique; | ||
In dichloromethane at 0 - 20℃; Inert atmosphere; | ||
With glacial acetic acid for 1h; Reflux; | ||
In ethanol; lithium hydroxide monohydrate at 70℃; for 0.0166667h; | A general procedure for reductive acetylation of nitroarenes General procedure: In a round-bottom flask (25 mL), a solution of nitrobenzene (0.123 g, 1 mmol) in H2O-EtOH (1.5:0.5 mL) was prepared. Magnetically, nanoparticles of NiFe2O4(at)Cu (0.15 g) were added, and the resulting mixture was stirred for 5 min. Afterward,NaBH4 (0.094 g, 2.5 mmol) was added and the resulting mixture was continued to stirring for 1 min at 70 °C. After reduction of nitrobenzene to aniline (monitored by TLC), Ac2O (0.204 g, 2 mmol) was added and the resulting mixture was stirred for 1 min at 70 °C. The nanocatalyst was separated by an external magnet, and the mixture was extracted with EtOAc (3 × 5 mL). The organic layer was dried over anhydrous Na2SO4. Evaporation of the solvent affords the pure acetanilide in 95% yield (0.128 g, Table 3,entry 1). | |
at 20℃; | ||
In dichloromethane at 0℃; | ||
at 20℃; | Acetanilides General procedure: Acetanilides were prepared according to the procedure of Dulla et al.38 Aniline or p-toluidine (15mmol) was added to a round bottomed flask containing acetic anhydride (21 mmol) and the reaction stirred atroom temperature for 30 min. Upon completion, the contents were poured in ice water, where white orcreamy precipitates were filtered and recrystallized in water. | |
In lithium hydroxide monohydrate | ||
With glacial acetic acid at 0℃; for 1h; | ||
With glacial acetic acid at 0 - 5℃; for 1h; | ||
at 20℃; for 3h; Inert atmosphere; | ||
In tetrahydrofuran at 20℃; | ||
In dichloromethane at 0 - 25℃; | ||
at 20℃; | General procedure for the preparation of acetanilide derivatives General procedure: To a mixture of aniline (2.0 mmol) was added acetic anhydride (6.0 mmol) and the reaction mixture was stirred at room temperature. The progress of the reaction was monitored by TLC. After the completion of the reaction, CH2Cl2 (20 mL) was added to the mixture. Then the organic solvent was washed with H2O (3×10 mL) and a saturated solution of NaHCO3 (20 mL) and dried over anhydrous Na2SO4. After removal of the solvent, the pure product was obtained. | |
In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With [bis(acetoxy)iodo]benzene In neat (no solvent) at 120℃; for 0.333333h; Microwave irradiation; Green chemistry; | |
89% | With nano-Fe3O4-supported sulfonic acid In neat (no solvent) at 120℃; for 2h; Green chemistry; | Aliphatic and Cyclic Amides 3a-d, 4a-d, 5a-c; General Procedure General procedure: Formamide/acetamide/phthalimide (1.0 mmol), aromatic/aliphatic amine (1.0 mmol) and Fe3O4-OSO3H (25 mg) were added to a round-bottom flask and heated at 120 °C for 2 h. After completion of the reaction, the products were isolated as described above. For compounds 3a-d, additional signals were observed in the 1H NMR spectra due to the presence of rotamers.30 |
86% | With sulfated tungstate In toluene for 12h; Reflux; Green chemistry; |
85% | With 1-(3-sulfopropyl)pyridinium phosphotungstate In neat (no solvent) at 120℃; for 0.833333h; Microwave irradiation; | 4.3.2. N-(p-Tolyl)acetamide (3b) General procedure: To a mixture of amide (2 mmol) and amine (2.6 mmol) ina 10 mL round bottomed ask was added [PyPS]3PW12O40 (140 mg, 0.04 mmol). The reaction mixture was stirred at the corresponding temperature under MW (700 W). The progress of the reaction was monitored by TLC. On completion, the mixture was diluted with ethyl acetate (20 mL) with stirring for 30 min. The insoluble catalyst was recovered by filtration or centrifugation. The filtrate was evaporated and the residue in almost pure form. Recrystallization or column chromatography could be used for further purication. |
85% | With Nd<SUB>2</SUB>Na<SUB>8</SUB>(OCH<SUB>2</SUB>CF<SUB>3</SUB>)<SUB>14</SUB>(THF)<SUB>6</SUB> at 120℃; for 10h; Inert atmosphere; Schlenk technique; | |
81% | With [Mn((N'1E,N'2E)-N'1,N'2-bis(phenyl(pyridin-2-yl)methylene)oxalohydrazide(-H))(OAc)(H2O)]2*6H2O In neat (no solvent) at 120℃; for 24h; | |
80% | With citric acid-coated magnetic Fe3O4 nanoparticles In neat (no solvent) at 120℃; for 8h; Inert atmosphere; | General procedure for the synthesis of products 3a-ac General procedure: To a mixture of catalyst (25.0 mg) and amide (1.0 mmol),amine was added (1.0 mmol) under an argon atmosphere,and the mixture was stirred at 120 °C for 8 h. After completion,the reaction mixture was allowed to cool to roomtemperature. It was then diluted with EtOAc and the catalystwas separated from the reaction mixture using an externalmagnet and washed twice with EtOAc, then all volatileswere removed under vacuum, and the resulting residue waspurified by column chromatography on silica gel to affordthe desired product. |
78% | In 1,4-dioxane at 20℃; for 0.5h; Microwave irradiation; Sealed tube; | General procedure: General procedure for the 1,4-dioxane mediated transamidation of amides with an amine under microwave. An oven-dried 10-mL microwave reaction vial containing a Teflon-coated magnetic stir bar was charged with carboxamide (1 mmol), amine (1 mmol), and dioxane (2 ml) (undried). The vessel was sealed with a plastic microwave septum, stirred at room temperature for 5 min and then placed into the MW cavity for a specified temperature and time. After the completion of reaction (TLC), the mixture was cooled to room temperature; distilled water (10 mL) was added to it and then extracted with ethyl acetate (3 10 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and then concentrated using a rotary vacuum evaporator. The crude product was purified by column chromatography using a mixture of ethyl acetate/n-hexane (10-20% of ethyl acetate depending upon the product) as an eluent |
77% | With Fe(OH)3 supported on Fe3O4 magnetic nanoparticles In para-xylene for 10h; Inert atmosphere; Reflux; Green chemistry; | |
75% | With graphene oxide at 150℃; for 24h; | III. General procedure of transamidation reaction General procedure: In a typical procedure, a mixture of amine (1 mmol), amide (1 mmol) and 50 mg GO was taken in a round-bottom flask (50 mL) and stirred the mixture using a magnetic stirring bar under open air at 150 °C for 24 h. After the reaction was completed, ethyl acetate (5 mL) was added to the reaction mixture and the catalyst was filtered off. The filtered catalyst was further washed with ethyl acetate and the combined organic layer was evaporated to afford nearly pure product. The residue was further purified by passing through a silica gel columnand eluting with ethyl acetate petroleum ether mixture. All products were characterized by spectral data as well as melting points (for solid compounds). |
74% | With [Ru-NHC] In toluene at 110℃; for 8h; Inert atmosphere; Schlenk technique; Sealed tube; | Representative procedure for transamidation reaction General procedure: A mixture of amide (5mmol), amine (5mmol), [Ru-NHC] complex (0.5mol%) and toluene (5mL) was stirred in a sealed tube under nitrogen atmosphere at 110°C for 8h. After cooling down to room temperature, the reaction solvent was removed under vacuum. After removal of the solvent, the crude reaction mixture was dissolved in CH2Cl2 and purified by column chromatography on silica gel (200-400mesh) eluting with heptane:ethanol [25:1] to give corresponding amides as a white solid. The yields are mentioned in Tables 3-5. The product was confirmed by NMR spectroscopy. Reported isolated yields are an average of two runs. |
66% | With <i>L</i>-proline In neat (no solvent) at 100℃; for 36h; Sealed tube; | |
65% | With C28H26ClN3ORuS In 1,4-dioxane at 100℃; for 8h; Sealed tube; Inert atmosphere; | 2.4 Representative procedure for transamidation reaction General procedure: A mixture of amide (5 mmol), amine (5 mmol) and catalyst (0.5 mol %) in 1,4 dioxane (5 mL) was stirred in a sealed tube under nitrogen atmosphere at 100 C for 8 h. Then the solvent was removed using rotavator and the resulting crude product was purified by column chromatography on silica gel (200-400 mesh) using eluents hexane and ethyl acetate [95:5, v/v] to afford corresponding amides as a white solid. The formation of products was confirmed by NMR spectroscopy. The reported isolated yields are an average of two runs. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.5% | ||
98% | With zinc(II) acetate dihydrate for 0.0166667h; Microwave irradiation; Sealed tube; chemoselective reaction; | |
98% | With palladium (II) nanoparticles supported on Schiff-base modified clinoptilolite nanocatalyst In neat (no solvent) at 20℃; for 0.333333h; Green chemistry; chemoselective reaction; | 2.4 General procedure for N-acylation of amines General procedure: Pd(at)MCP (0.012g) was added to a mixture of amine (1mmol) and acetic acid (1.2mmol) and the whole mixture was stirred in a round bottomed flask at room temperature for the appropriate time (Table 3). The reaction progress was followed by GC and TLC (eluent, n-hexane:ethyl acetate, 4:1). After completion of the reaction, EtOAc (10mL) was added to the reaction mixture, and the resulting mixture filtered. The filtrate was washed with 1M HCl (3×5mL) and then the organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuum to obtain pure N-acylated products. |
97% | at 150℃; microwave irradiation; | |
97% | With magnesia In neat (no solvent) at 70℃; for 0.25h; Green chemistry; chemoselective reaction; | General procedure for the synthesis of amides General procedure: In an oven dried round bottomed flask (50 mL) nano-MgO (5.0 mol%) were added and then alky/aryl amines (5.0 mmol) and aromatic/aliphatic acid (5.0 mmol) was added. After that it was allowed to stir on a pre heated oil bath at 70 °C under aerobic condition till the required time (the progress of the reaction was judged by TLC). After the completion, the reaction mixture was brought to room temperature and ethyl acetate (3 × 10 mL) was added to it and then centrifuged at 3500 rpm to recover the nano catalyst. Having done this, the reaction mixture was washed with water and brine, dried over anhydrous Na2SO4, concentrated in a rotary evaporator and finally the crude product was charged to column chromatography (ethylacetate:hexane (3:7) as an eluent) for purification and wherever necessary the products were recrystallized from hot ethanol. |
94% | With hydrazine hydrate for 3h; Heating; | |
94% | With (1-methyl-3-(3-sulfopropyl)-1H-imidazol-3-ium)3[PW12O403-] In neat (no solvent) at 100℃; for 0.0833333h; Green chemistry; | 4.4 General procedure for the synthesis of amides (Table 3) General procedure: To a mixture of amine (2 mmol) and carboxylic acid (6 mmol) in a 10 mL round bottomed flask was added [MIMPS]3PW12O40 (140 mg, 0.04 mmol). The reaction mixture was stirred at 100 °C. The progress of the reaction was monitored by TLC. On completion, the mixture was diluted with ethyl acetate (20 mL) with stirring for 30 min. The insoluble catalyst was recovered by filtration. The filtrate was washed with satd solution of NaHCO3 (5 mL×3), brine, and dried over anhyd Na2SO4. The solvent was evaporated and the residue in almost pure form. Recrystallization or column chromatography could be used for further purification. |
94% | With alum doped nanopolyaniline at 100℃; for 1h; Green chemistry; | 2.3. General procedure for acylation of alcohols and amines General procedure: In a typical reaction procedure, substituted alcohols (1.5 mmol) oramines (1.5 mmol) with acetic acid (3 mmol) were taken in to 50 mLround bottom flask and 0.037 g (0.3 mol %) of NDPANI catalyst added tothe reaction mass. The reaction was maintained at 100 C with constantstirring. The progress of the reaction was monitored by TLC. Aftercompletion of the reaction, the catalyst was recovered from the reactionmixture by simple filtration and washed several times with ethyl acetate,then dried in the oven for reuse. To remove excess acetic acid, saturatedsolution of NaHCO3 was added to the reaction mixture. The product wasextracted with chloroform and the organic layer was dried by usinganhydrous Na2SO4 and evaporated under vacuum. In few cases thecrude product was then subjected to a short silica bed with hexane andethyl acetate (8:2) mixture to eluate the corresponding acetate/amideproducts in high purity. All the products were characterized by using 1HNMR and 13C NMR spectra. |
92% | With 2-methyl-1-butylimidazolium trifluoroacetate In neat (no solvent) at 70℃; for 8h; | General experimental procedure General procedure: To a magnetically stirred mixture of HCO2H (0.76 g, 14 mmol, 85%) and IL-III (126 mg, 0.5 mmol) was added N-allyl-N-benzyl amine (1.470 g, 10 mmol, Table 2, entry 6) and then the reaction mixture was heated in an oil bath at 70 °C. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was diluted with water (10 ml) and extracted with ether (10 ml ×3). The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and evaporated to give residue under reduced pressure. The crude product was passed through a short pad silica-gel column (in order to remove any trace amount of ionic liquid left in the product) by elution with diethyl ether. The evaporation of the solvent under reduced pressure, dried under high vacuum afforded light yellowish sticky solid. The identity of the products was confirmed by IR, 1H, 13C NMR and mass spectroscopy. |
92% | With 1-methyl-3-(4-sulfonylbutyl)-1H-imidazol-3-ium trifluoromethanesulfonate at 90℃; for 0.133333h; Microwave irradiation; chemoselective reaction; | Typical procedure for N-acylation Amines (microwave irradiation): General procedure: A mixture of amines (0.01 mol), acetic acid (0.015 mol, 1 mL) and [BMIM(SO3H)][OTf] (50 mol %) was introduced into a Biotage microwave oven and heated for 6 to 9 minutes at 90oC. Progress of the reaction was monitored by TLC and GC-MS. After completion of reaction, the reaction mass was cooled at room temperature and poured into ice water. The crystals of N-acylated product so obtained were filtered, washed with of cold ethanol-water mixture (10-15mL) and dried. |
91.6% | In acetonitrile for 8h; Heating; | |
91% | With ZnO nanofluid at 110℃; for 2.5h; neat (no solvent); | |
90% | for 0.25h; microwave irradiation; | |
90% | With magnatic matariel from fly ash In neat (no solvent) for 1h; Reflux; | |
for 3h; Heating; Yield given; | ||
With thionyl chloride | ||
at 110℃; for 2h; | ||
With phosphoric acid | ||
at 20℃; for 0.333333h; | ||
With phosphoric acid Reflux; | ||
With phosphoric acid | ||
With zinc In water at 100℃; for 0.666667h; | 1 Example 1 80 mL of toluene was added to a 500 mL three-necked flask, and 5 mL of 90% sulfuric acid and 8 mL of 65% nitric acid were added slowly and reaction temperature was controlled at 30 for 20 min to obtain p-nitrotoluene,The temperature was raised to 70 ° C, and the mixture was added dropwise with 2 mL of 20% hydrochloric acid solution into a three-necked flask. After the addition, 0.2 g of tin powder and 5 mL of 40% sodium hydroxide solution were added and stirred for 20 min. To obtain p-toluidine;The obtained p-toluidine was added with 50 mL of water, 0.1 g of zinc powder and 30 mL of glacial acetic acid. The mixture was stirred and heated in a water bath to 100 ° C. After 40 minutes of reaction, 5 mL of acetic anhydride was added, and the white mist was stopped in the beaker. Heating, the beaker will be hot in the reaction under the stirring slowly into the 70mL of cold water, and stirring, followed by suction filtration to p-methyl acetanilide; 5 g of p-methylacetanilide solid was added to a 250 mL beaker,To the beaker was added 150 mL of water and 10 g of magnesium sulfate,Water bath heated to 83 ° C, while the alcohol lamp heating preparation 5g potassium permanganate 25mL water solution to boiling dissolved,The hot potassium permanganate solution was added to the beaker in portions over 25 minutes with vigorous stirring,After the addition was continued, stirring was continued at this temperature for 10 min,After the hot filter paper with double filter,The filtrate was boiled with 1 mL of ethanol and then filtered. The filtrate was cooled to 20 ° C,To the filtrate by adding 20% sulfuric acid to adjust the pH value of 1, filtered solid,Rinse with ice water, filtered to ethyl p-nitro-benzoate; The resulting solid of ethyl p-nitrobenzoate was placed in a 250 mL dry three-necked flask and heated to 70 ° C in an oil bath to completely melt the solid. Thereafter, the temperature was raised to 90 ° C and a constant flow of dry chlorine gas was passed therethrough.Dichloro-p-nitrobenzoic acid ethyl ester was obtained after stopping the reaction for 8 min.Take 18g of reaction product into the Erlenmeyer flask, add 120mL of water, 6gNaBrO3 and 40mL of dibromomethane, and slowly add 4mL of 47% hydrogen bromide with stirring. Stir the reaction for 10min, separate the layers and extract the organic phase Distilling and crystallizing to obtain ethyl 2-chloro-6-bromo-p-nitrobenzoate; adding ethyl 2- chloro-6-bromo-p-nitrobenzoate as a solid, adding sodium hydroxide solution with 15-20% Soak 10min, standing filter,Adding the solid to the carbon tetrachloride solution to soak, soaking and then removing the solvent by distillation, putting the crystal into an ice bath to cool down to 5 DEG C to obtain crystal, filtering and drying to obtain 2-chloro-6-bromo-p-nitrobenzoic acid. | |
With phosphoric acid Reflux; | ||
With phosphoric acid for 6h; Reflux; | 3.2. Preparation of Acetanilides 2a-f General procedure: Orthophosphoric acid (0.2 mol) was added to a stirred solution of substituted anilines1a-f (1.0 mol) in glacial acetic acid (2.0 mol, 118 mL) and the resulting mixture was heatedto reflux for 6 h. After the completion of the reaction, the mixture was poured into ice coldwater with continuous stirring. The precipitated solid was filtered off, washed with excesscold water, and recrystallized from boiling water to produce acetanilides 2a-f [45]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With ammonium molybdate; lithium hydroxide monohydrate; HNO3 In chloroform for 6h; Heating; | |
87% | With potassium peroxodisulfate; silver(I) nitrite; NaNO2 In acetonitrile at 110℃; for 16h; regioselective reaction; | |
84% | With tetrammine copper(II) sulphate; HNO3 In dichloromethane; lithium hydroxide monohydrate at 20℃; for 2h; regioselective reaction; |
78% | With tert.-butylnitrite at 25℃; for 4h; | 2 Add 0.2 mmol of p-methylacetanilide, 0.6 mmol of tert-butyl nitrite, 2 mL of hexafluoroisopropanol and a No. 5 reaction magnet into the reactor and mix in sequence, pass the condensed water through the condensing tube from bottom to top, and set the temperature at 25°C. Stirring the reaction for 4h to obtain a reaction solution containing 2-nitro-4-methylacetanilide compound; further, the speed of the stirring reaction is 500 rev/min.This example also includes further purification of the 2-nitro-4-methylacetanilide compound: pour the reaction solution containing the 2-nitro-4-methylacetanilide compound into a separatory funnel, add 15 mL of distilled water, and use 10 mL of Ethyl acetate was extracted three times, and the organic phase was distilled under reduced pressure to obtain a crude product, which was separated and purified by column chromatography to obtain a 2-nitro-4-methylacetanilide compound with a yield of 78%. |
53% | With sulfuric acid; HNO3 for 2h; Cooling; | 14 4.1.14 N-(4-Methyl-2-nitrophenyl)acetamide (20) To nitrosonitric acid (160 mL) was added 19 (39.5 g, 0.265 mol) in batches at 5 °C and stirred for 2 h. Then the mixture was poured slowly to ice water (1 L) while stirring constantly. The resulting precipitate was filtered and recrystallized from ethanol to give product 20 (27 g, 53%) as yellow acicular crystal. Mp: 91-92 °C (lit. |
53% | With potassium peroxodisulfate; NaNO2 In acetonitrile at 120℃; for 12h; Inert atmosphere; Schlenk technique; | General procedure (taking the synthesis of 2a as an example) General procedure: A 10-mL screw-capped Schlenk tube, equipped with a magnetic stirring bar, was charged under argon with N-(4-(tert-butyl)phenyl)acetamide 1a (38 mg, 0.2mmol), NaNO2 (17 mg, 0.24mmol), and K2S2O8 (162 mg, 0.6mmol), followed by the addition of MeCN (2.0mL). The tube is sealed and the mixture was stirred at 120 °C for 12 h; then it was quenched with saturated aqueous Na2S2O3 (1.0mL) and water (10.0mL), and extracted with CH2Cl2 (10.0mL) three times. The residue obtained after evaporation of the solvent was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 24:1, v/v) to afford N-(4-(tert-butyl)-2-nitrophenyl)acetamide 2a as a pale yellow solid (36 mg, 76% yield). |
50% | With iron (ΙΙΙ) nitrate nonahydrate; NHPI In 1,2-dichloro-ethane at 50℃; for 10h; regioselective reaction; | |
With HNO3 | ||
With HNO3; glacial acetic acid | ||
With hydrogenchloride; sulfuric acid; HNO3 | ||
With sulfuric acid; HNO3 1.) 0 deg C, 10 min, 2.) RT, 30 min; | ||
With HNO3 In acetic anhydride at 10 - 12℃; for 2.5h; | 4-Methyl-2-nitroaniline (4a) and 2-methyl-6-nitroaniline (4b) A slightly modified procedure of Howard was applied [27]. Toluidine (1a or 1b; 53.5mL, 0.5mol) was introduced, in small portions and under constant stirring, to Ac2O (325mL). The obtained solution was cooled to 12-13°C in an ice-salt bath. After that, under stirring and at a rate which maintained the temperature within the limits of 10-12°C, 70% HNO3 (63mL) was added dropwise to the reaction mixture. The addition was completed in 2.5h and the solution was poured, with stirring, into 1.5L of ice-water. The precipitate (cream-colored solid) of acetamide (3a, or mixture of 3b and 3c) was collected on a Büchner funnel, washed with four 250-mL portions of ice-water and partially dried by suction. The moist acetamide (3a, or mixture of 3b and 3c) was mixed with 70% H2SO4 (100mL) and stirred at reflux for 3h. The hydrolysis product of acetamide 3b, 2-methyl-6-nitroaniline (4b), was isolated from the reaction mixture by steam distillation. The bright orange needles of 4b, which separated when the distillate was cooled, were collected on a Büchner funnel and dried in a vacuum desiccator. In the case of the hydrolysis of acetamide 3a, the warm reaction mixture was diluted with 350mL of water and made alkaline with 10% aq. NaOH. After cooling to room temperature 4-methyl-2-nitroaniline (4a) precipitated as a brown powder that was separated by vacuum filtration, washed with three 200-mL portions of water, and dried in a vacuum desiccator. The yield was 53.6% (40.73g) and 52.3% (39.78g) for compounds 4a and 4b, respectively. | |
With HNO3; glacial acetic acid at -10 - 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sulfuric acid; nitric acid | |
41% | With sodium nitrate; dipotassium peroxodisulfate In acetonitrile at 140℃; for 24h; Inert atmosphere; Schlenk technique; | General procedure (taking the synthesis of 2a as an example) General procedure: A 10-mL screw-capped Schlenk tube, equipped with a magnetic stirring bar, was charged under argon with N-(4-(tert-butyl)phenyl)acetamide 1a (38 mg, 0.2mmol), NaNO2 (17 mg, 0.24mmol), and K2S2O8 (162 mg, 0.6mmol), followed by the addition of MeCN (2.0mL). The tube is sealed and the mixture was stirred at 120 °C for 12 h; then it was quenched with saturated aqueous Na2S2O3 (1.0mL) and water (10.0mL), and extracted with CH2Cl2 (10.0mL) three times. The residue obtained after evaporation of the solvent was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 24:1, v/v) to afford N-(4-(tert-butyl)-2-nitrophenyl)acetamide 2a as a pale yellow solid (36 mg, 76% yield). |
With nitric acid |
With nitric acid | ||
(nitration); | ||
With nitric acid at -70 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With NBS; diphenyldisulfane In acetonitrile at 20℃; for 2.5h; | |
99% | With copper (II) acetate; palladium diacetate; copper (II) bromide at 120℃; for 1h; neat (no solvent, solid phase); | |
99% | With copper (II) acetate; copper (II) bromide at 120℃; for 1h; Neat (no solvent); |
98% | With Bromoeosine; 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) In acetonitrile at 25℃; for 1h; | |
95% | With hydrogen bromide; dihydrogen peroxide In lithium hydroxide monohydrate at 20℃; for 24h; Darkness; | |
95% | With hydrogen bromide; sodium bromide In chloroform; lithium hydroxide monohydrate at 10 - 25℃; Electrolysis; regioselective reaction; | General Procedure for Electrochemical Bromination General procedure: A solution of 4-methoxy toluene (0.625 g, 5 mmol) in 25ml chloroform wastaken in a beaker-type undivided cell. A 25% aqueous sodium bromide solution(50 ml) containing 5ml of 47% HBr was added to it. Platinum electrodes (each of10 cm2 area) were placed in the upper layer of the aqueous phase. The organic phasealone was stirred with a magnetic stirrer at a rate of 40 rpm in such a way that theorganic layer did not touch the electrodes. The electrolysis was conducted galvanostaticallyat a current density of 30mA=cm2 until the quantity of charge indicated inTable 1 was passed at 15 C.After completion of electrolysis, the lower organic phase was separated,washed with 10% sodium thiosulfate solution followed by water (225 ml), anddried with anhydrous Na2SO4. The solvent was removed under reduced pressureto afford 1.46 g (86% yield) of 3-bromo 4-methoxy benzylbromide as product. |
95% | With hydrogen bromide; 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) In lithium hydroxide monohydrate at 20℃; for 0.0833333h; regioselective reaction; | II. Bromination of anilides 1 1a as example: To a stirred suspension of N-(p-tolyl)acetamide 1a (75 mg, 0.5 mmol) and Selectfluor (213 mg, 0.6 mmol) in water (3.0 mL) was added HBr (40% aqueous, 0.08 mL, 0.55 mmol), and the mixture was stirred for 5 min at room temperature. After 1a was consumed, as indicated by TLC, the reaction mixture was quenched with saturated aqueous Na2S2O3 (2.0 mL) and water (20.0 mL), and extracted with CH2Cl2 (10.0 mL) three times. The residue obtained after evaporation of the solvent was purified by column chromatography on silica gel (petroleum ether-ethyl acetate = 6:1, v/v) to afford N-(2-bromo-4-methylphenyl)acetamide 2a as a white solid (108 mg, 95% yield). |
94% | With NBS; palladium diacetate; toluene-4-sulfonic acid In toluene at 20℃; for 1h; chemoselective reaction; | |
93% | With NBS In lithium hydroxide monohydrate at 25℃; for 23h; ambient light; | |
92% | With NBS In acetonitrile for 2h; Irradiation; regioselective reaction; | |
91% | With silica-supported quinolinium tribromide In acetonitrile at 80℃; for 12h; regioselective reaction; | |
90% | With lithium hydroxide monohydrate; bromine In dichloromethane at 20℃; for 6.5h; UV-irradiation; | |
88% | With NBS; methanesulfonic acid; NiCl2·6H2O In lithium hydroxide monohydrate at 20℃; for 5h; Sealed tube; Microwave irradiation; Green chemistry; regioselective reaction; | Procedure B General procedure: A 10 mL microwave vial was charged with an anilide or carbamate derivative (1.0 equiv, 0.5 mmol), NXS (1.2 equiv, 0.6 mmol), Ag2CO3 (10 mol%, 14 mg), MSA (3.0 equiv, 1.5 mmol, 144 mg) and toluene (2.0 mL). The vial was then sealed and stirred at 50 °C, for 8 h. After the reaction time, the mixture was diluted with EtOAc and washed with sodium bicarbonate solution. The organic layer was dried with anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (n-hexane/EtOAc) to give the desired product. |
86% | With sodium wolframate; sodium perborate; sulfuric acid; acetic anhydride; potassium bromide In glacial acetic acid for 1h; Ambient temperature; | |
85% | With NBS; cobalt(II) 2,4-pentanedionate; trifluoroacetic acid; silver(I) oxide In 1,2-dichloro-ethane at 60℃; for 16h; regioselective reaction; | |
83% | With NBS; palladium diacetate; copper(II) bis(trifluoromethanesulfonate) In 1,2-dichloro-ethane Inert atmosphere; Sealed tube; regioselective reaction; | |
77% | With ammonium molibdate; dihydrogen peroxide; glacial acetic acid; potassium bromide for 1h; Ambient temperature; | |
76% | With bromine; glacial acetic acid | |
73% | With NBS; bis[dichlorido(η5-1,2,3,4,5-pentamethyl-cyclopentadienyl)iridium(III)]; <i>N</i>-<i>tert</i>-butoxycarbonyl-<i>L</i>-phenylalanine; silver(I) bis(trifluoromethanesulfonyl)imide In 1,2-dichloro-ethane at 20℃; for 4h; Inert atmosphere; Sealed tube; | |
With perchloric acid; mercury (II) acetate; N-bromoacetamide In lithium hydroxide monohydrate at 35℃; δE(excit.), ΔH(excit.), ΔS(excit.); further reaction partners: Cl(-), Br(-); | ||
With bromine In lithium hydroxide monohydrate at 25.4℃; energy of activation, entropy of activation, frequency factor; | ||
beim Bromieren; | ||
With lithium hydroxide monohydrate; hydrogen bromide; dihydrogen peroxide | ||
With hydrogenchloride; bromine; glacial acetic acid | ||
With bromine | ||
With bromine In glacial acetic acid at 55℃; Yield given; | ||
Multi-step reaction with 2 steps 1: diluted KHCO3; hypobromous acid / <0 2: 95 °C | ||
3.16 g | With NaBrO3; hydrogen bromide at 20℃; for 0.5h; | |
With bromine In glacial acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With chlorosulfonic acid at 0 - 100℃; for 2.16667h; | 4.1.3.5. N-(3-(2-((5-Cyanopyrazolo[1,5-a]pyridin-3-yl)methylene)-1-methylhydrazinylsulfonyl)-4-methylphenyl)acetamide (6e) N-p-Tolylacetamide (500 mg, 3.35 mmol) was added portionwise to ClSO3H (1.3 mL, 20 mmol) at 0 °C. After 10 min, the reaction mixture was heated to 100 °C for 2 h. The solution was dripped slowly onto ice and stood until all of the ice had melted. Then the oily product was extracted twice with CH2Cl2, the combined extracts were dried (Na2SO4) and the solvent removed in vacuo to leave 5-acetamido-2-methylbenzenesulfonyl chloride as an off-white solid (636 mg, 77%). 1H NMR δ (400 MHz, d6-DMSO) 9.86 (br s, 1H), 7.79 (d, J = 2.3 Hz, 1H), 7.59 (dd, J = 8.1, 2.3 Hz, 1H), 7.02 (d, J = 8.1 Hz, 1H), 2.44 (s, 3H), 2.00 (s, 3H). NOESY’s were observed from the signal at 9.86 to 7.79, 9.86 to 7.59, and 2.44 to 7.02. LC-MS (APCI+) 248 (MH+ with 35Cl, 100%), 250 (MH+ with 37Cl, 30%). Reaction of 2 (30 mg, 0.18 mmol) and the above sulfonyl chloride (87 mg, 0.35 mmol) using NaHCO3, after chromatography (eluting with CH2Cl2:MeOH 99:1 to 98.5:1.5) gave 6e as a yellow solid (48 mg, 67%). |
75% | With chlorosulfonic acid at 20 - 60℃; for 1h; | 2 Production of 3-chlorosulfonyl-4-methylacetoanilide 130 g (871 mmol) of p-acetotoluidine was gradually added to 405 g (3,477 mmol) of chlorosulfonic acid at room temperature, followed by stirring at 60°C for 1 hour. The reaction mixture was allowed to stand at room temperature and then poured into ice water. Extraction with ethyl acetate was conducted. The organic phase obtained was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 162 g (yield: 75%) of 3-chlorosulfonyl-4-methylacetoanilide. 1H-NMR (300 MHz, CDCl3/TMS δ (ppm)) 2.22 (3H, s), 2.73 (3H, s), 7.37 (2H, d), 7.50 (1H, brs), 8.00 (1H, s), 8.02 (1H, d) |
70% | With chlorosulfonic acid for 0.75h; Heating; |
With chlorosulfonic acid at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With chlorosulfonic acid In toluene at 90℃; for 0.5h; | |
99% | With p-toluenesulfonyl chloride; zinc(II) chloride In acetonitrile for 1h; Inert atmosphere; Reflux; | |
99% | With aminosulfonic acid; zinc(II) chloride In acetonitrile at 90℃; for 0.75h; |
99% | With iodine In acetonitrile for 1h; Reflux; | |
97% | With 2,2,4,4,6,6-hexachloro-1,3,5-triaza-2,4,6-triphosphorine In acetonitrile at 80℃; for 2h; | |
97% | Stage #1: 4-methylacethophenone oxime With fluorosulfonyl fluoride; triethylamine In acetonitrile at 20℃; Stage #2: With hydrogenchloride In water; acetonitrile at 20℃; | |
96% | With oxalyl dichloride at 0 - 20℃; for 2h; | 4.2 Typical procedure for synthesis of compound 2a General procedure: Polystyrene-supported phosphine oxide (10.4 mg, 2.5 mol%), (E)-1-Phenylethan-1-one oxime 1a (67.5 mg, 0.5 mmol) and HFIP (2 mL) were added to a 10-mL glass vessel containing a magnetic stirring bar. Then, oxalyl chloride (64.8 mg, 0.5 mmol) was added at 0 °C. The mixture was stirred at room temperature for 2 h. After completion of the reaction (indicated by TLC), the catalyst was removed by filtration and the solvent was removed under reduced pressure. The crude material was purified by silica gel column using PE/EtOAc as the eluent to afford the desired product 2a in 99% yield. |
95% | With mesoporous silica chloride (SBA-Cl) In toluene for 3h; Reflux; | |
95% | With boron trifluoride diethyl etherate In acetonitrile for 3h; Inert atmosphere; Reflux; | |
95% | With iodine; triphenylphosphine In acetonitrile for 0.166667h; Reflux; | |
94% | With 1,3-dimethylimidazolium sulfate monomethyl ester; p-toluenesulfonyl chloride at 50℃; for 4.5h; | |
94% | With tartaric acid at 180℃; for 0.05h; Microwave irradiation; Green chemistry; | |
94% | With C82H80N4O6; mercury dichloride In tetrahydrofuran; water; acetonitrile at 20℃; for 0.416667h; | |
94% | With carbon tetrabromide; N,N-dimethyl-formamide In acetonitrile for 12h; Inert atmosphere; Irradiation; Sealed tube; | |
93% | With carbon tetrabromide; Eosin Y; N,N-dimethyl-formamide In acetonitrile at 20℃; for 14h; Irradiation; Inert atmosphere; Green chemistry; | General Procedure for the Visible-Light-Driven Beckmann Rearrangement General procedure: A mixture of ketoxime 1 (1.0 mmol), CBr4 (2.0 equiv), eosin Y (2 mol%), DMF (20 mol%) and MeCN (3 mL) was taken in a hot oven dried round bottom flask and irradiated with green LEDs under a nitrogen atmosphere. After completion of the reaction as indicated by TLC, it was quenched with saturated aqueous sodium hydrogen carbonate (10 mL) and extracted with ethyl acetate (3 × 10 mL). The organic phase was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to yield the crude product, which was purified by silica gel column chromatography (EtOAc-hexane) to give the corresponding amide 2 in high yield. All the products are known compounds and were characterized by comparison of their mp, TLC, 1HNMR, 13C NMR and MS data with authentic samples obtained commercially or prepared byliterature methods. |
92% | With diethyl chlorophosphate In toluene for 0.416667h; Heating; | |
92% | With tricarallylic acid at 160℃; for 0.0833333h; Inert atmosphere; neat (no solvent); | |
92% | With tin(II) chloride dihdyrate; tetra-(n-butyl)ammonium iodide In acetonitrile for 1h; Molecular sieve; Reflux; | |
92% | With trifluoromethylsulfonic anhydride In dichloromethane at 20℃; for 2.5h; Inert atmosphere; | |
92% | With ammonium peroxydisulfate; dimethyl sulfoxide In 1,4-dioxane at 100℃; for 1h; Schlenk technique; Inert atmosphere; | |
90% | With iron(III) chloride at 85℃; for 2h; | |
90% | With aluminium trichloride; silica gel; zinc(II) chloride In dichloromethane for 0.116667h; microwave irradiation; | |
90% | With aluminum (III) chloride In acetonitrile for 2h; Inert atmosphere; Reflux; | |
90% | With 2-chloro-1-methyl-pyridinium iodide; triethylamine In acetonitrile at 20℃; for 0.5h; | Typical Procedure for the Beckmann Rearrangement of Acetophenone Oxime Using Mukaiyama Reagent: General procedure: A suspension of acetophenone oxime (0.135 g, 1 mmol),Mukaiyama reagent (0.383 g, 1.5 mmol), and Et3N (0.21 mL,1.5 mmol) in CH3CN (3 mL) was magnetically stirred atroom temperature. After completion of the reaction (monitoredby TLC) and evaporation of CH3CN, aqueous HCl(5%, 10 mL) was added and the organic layer extracted withCH2Cl2 (3 × 5 mL). The combined organic extracts weredried over Na2SO4, filtered, and concentrated. Purification ofthe crude product by short column chromatography on silicagel (n-hexane/EtOAc, 5/2) provided N-phenylacetamide(0.120 g, 89%) as a white solid: |
90% | With 1-methylimidazole hydrogen sulfate; phosphorus pentoxide In neat (no solvent) at 90℃; for 6h; Inert atmosphere; | 3.3. 1.1. General Procedures for the Synthesis of Amides 3a-3o General procedure: To a solution of the oxime substrates 2a-2o (9.50 mmol) in (HMIm)HSO4 (2.05 g, 11.4 mmol), the co-catalyst P2O5 (0.15 g, 1.0 mmol) was added. Then the solution was heated to 90 °C and the reaction was monitored by TLC. After completion of the reaction, the mixture was extracted with ethyl acetate (50 mL) twice, and the combined organic phase was washed with the aqueous solution of sodium bicarbonate and brine, dried over anhydrous Na2SO4 and concentrated in vacuo to afford a residue, which was purifi ed by column (ethylacetate: petroleum ether = 1:4) to afford the products 3a-3o. 3a [22]: White solid, Yield: 91%. m.p.: 127.0-128.0 C; 1H-NMR (600 MHz, DMSO-d6) δ 9.80 (brs, 1H), 7.51-7.46 (m, 2H), 7.20 (d, J = 7.9 Hz, 1H), 6.89-6.84 (m, 2H), 3.71 (s, 3H), 2.01 (s, 3H); 13C-NMR (150 MHz, DMSO-d6) δ 168.2, 155.5, 133.0, 121.0, 114.2, 55.6, 24.3; HRMS(+): calcd. for C9H11NO2 [M + H]+ 166.0863, found 166.0859; calcd. for C9H11NO2Na [M + Na]+ 188.0682, found 188.0682. |
90% | With 10-methyl-9-phenylacridin-10-ium perchlorate In 1,2-dichloro-ethane at 20℃; for 5h; Irradiation; Sealed tube; | |
88% | With thionyl chloride; fipronilβ-cyclodextrin In water; acetone at 80℃; for 0.133333h; | |
87% | With ytterbium(III) triflate In acetonitrile for 6.5h; Heating; | |
87% | With ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate In acetonitrile at 85℃; Microwave irradiation; Inert atmosphere; | |
86% | With O-phenyl phosphorodichloridate In acetonitrile at 20℃; for 1h; | |
85% | With chlorotropylium chloride In acetonitrile at 80℃; for 0.166667h; Inert atmosphere; | |
84% | With indium(III) triflate for 0.00833333h; Microwave irradiation; Ionic liquid; | |
83% | With carbon tetrabromide; triphenylphosphine In toluene at 80℃; for 0.5h; Inert atmosphere; | |
82% | With hydroxylamine hydrochloride; oxalic acid at 120℃; for 15h; | |
80% | With dihydrogen phosphate for 0.0166667h; microwave irradiation; | |
78% | With phosphotungstic acid In acetonitrile for 2.16667h; Reflux; Green chemistry; chemoselective reaction; | General procedure: all the oximes were prepared as per reported in theliterature30. The oxime (5 mmol) was dissolved in acetonitrile (5 ml) in a roundbottom flask (RBF) followed by addition of DTPA (0.05 mmol) catalyst. Thereaction mixture was refluxed until completion of the reaction as indicated byTLC. On completion, the reaction mixture was cooled down and excess ofsolvent was removed under vacuum which resulted in separation of crudeproduct. Then the water (2-3 ml) was added to crude product, stirred andfinally it was filtered. The process was repeated three times and filtrate havingcatalyst was evaporated under vacuum at 70 C which resulted in separation ofcatalyst. The products were recrystallized from methanol and characterized byFT-IR, 1H NMR, 13and C NMR spectroscopic techniques. Spectral data:Benzanilide (entry 1): white crystalline solid, mp 161-164 C. FT-IR (KBr)cm1: 3343(N-H stretch), 1655 (CO stretch), 3051 (C-H stretch of Ar). 1HNMR (400 MHz, DMSO, d ppm): 10.1(1H, s, NH), 7.6-7.0 (5H, m, Ar-H), 8.0-7.4(5H, m, Ar-H). 13C NMR (400 MHz, DMSO, d ppm): 164.8, 135.9, 134.2, 132.2,129.0, 129.0, 128.9, 128.9, 127.5, 127.5, 124.4, 121.6, 121.6. |
75% | With tris(2,2'-bipyridyl)ruthenium dichloride; carbon tetrabromide; N,N-dimethyl-formamide at 50℃; for 0.833333h; Flow reactor; | |
74% | With montmorillonite KSF; montmorilonite In toluene for 6h; Heating; | |
With perchloric acid supported over silica In dichloromethane at 20℃; for 9h; | ||
With 7,7-dichlorocyclohepta-1,3,5-triene In acetonitrile at 80℃; Schlenk technique; Inert atmosphere; | 4 Example 4 In a 50 ml three-necked round-bottomed flask, 0.149 g of p-methylacetophenone oxime and 8 mg of 1,1-dichlorocycloheptene were charged, followed by a bulb-type condenser, and the gas was evacuated on a Schlenk three times , The system to maintain N2 atmosphere, and then add 10ml of acetonitrile, stirred and heated to 80 ° C reflux reaction, followed by liquid chromatography analysis of the reaction (after the sample was added to the sample a little acetic acidEthyl ester): The conversion of raw materials was 62% at 3 min, the conversion of raw materials was complete within 10 min, the selectivity of acetyl-p-methylaniline was> 98%. After completion of the reaction, the solvent was distilled off under reduced pressure and the pure acetyl-p-methylaniline was obtained as a white solid by flash chromatography. 1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With Methyl formate at 180℃; for 8h; | |
58% | With sodium sulfite for 16h; Reflux; | General procedure for the preparation of anilides from nitroarenes General procedure: A mixture of aromatic nitro compound (10 mmol), sodium sulfite (35 mmol) and carboxylic acid (80 mmol) wasrefluxed for 16 hours. The reaction mixture was poured to a mixture of ethyl acetate (50 mL) and water (50 mL). Organicphase was separated, dried on sodium sulfate and evaporated to produce crude product. The product was purified bycolumn chromatography or by re-crystallization in the mixture of methanol : water (1:1). Furthermore, it is important tonote that this methodology is scaled-up to kilogram scale without any difficulty. For this obJective, the acetaminophen andpropanil was prepared in 10 mole scale with technical grade 4-nitrophenol and 3,4-dichloronitrobenzene, acetic acid andpropionic acid respectively. |
52% | With carbon monoxide; tin(IV) chloride In 1,4-dioxane at 180℃; for 4h; |
92 %Chromat. | With hydrogen at 100℃; for 24h; Sealed tube; regioselective reaction; | |
With potassium phosphate; hydrogen Irradiation; chemoselective reaction; | ||
With potassium phosphate; hydrogen for 24h; Irradiation; | 4 In a self-made reaction tube with a cooling system, add 10 mg of 3% Pt/N-TiO to 3 ml of acetic acid solution in benzene2/Ti3C catalyst, K3PO4(1 mmol) and 1 mmol p-nitrotoluene. Before the reaction, use 1 atm H2saturation.Thereaction was carried out for 24 hours undercommercial 0.75 Wcm-2blue LED light, the conversion rate of p-nitrotoluene was 100.0%, and the selectivity of amidation products was 100.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With trichlorophosphate at 0 - 90℃; | General procedure for the synthesis of quinolinederivatives (6a-d) General procedure: To a solution of dimethylformamide (3 eq) in a flaskequipped with a drying tube at 0 °C, phosphorus oxychloride(POCl3) (7 eq) was added dropwise with stirring.Then, to this solution, add acetanilide derivatives (1 mmol).The reaction mixture was stirred and refluxed at 80-90 °Cfor a time ranging between 4 and 15 h. After the completionreaction, the mixture was cooled and poured in ice-coldwater and stirred for 30 min, and then filtered and washedwell with water and dried. The compounds were purified byrecrystallization from either ethyl acetate. 2-Chloro-3-formyl-6-mthylquinoline (6b)It was obtained as a yellow powder. Yield: 92%; 1H-NMR(400 MHz, DMSO-d6) δ 10.36 (s, 1H), 8.83 (s, 1H), 8.00 (t,J = 1.4 Hz, 1H), 7.92 (d, J = 8.6 Hz, 1H), 7.82 (dd, J = 8.6,2.0 Hz, 1H), 2.55-2.49 (m, 3H); 13C-NMR (101MHz,DMSO-d6) δ 189.88, 148.54, 147.66, 141.03, 138.56,136.44, 129.13, 127.96, 126.77, 21.51. |
92% | With trichlorophosphate at 0 - 90℃; | General procedure for the synthesis of quinolinederivatives (6a-d) General procedure: To a solution of dimethylformamide (3 eq) in a flaskequipped with a drying tube at 0 °C, phosphorus oxychloride(POCl3) (7 eq) was added dropwise with stirring.Then, to this solution, add acetanilide derivatives (1 mmol).The reaction mixture was stirred and refluxed at 80-90 °Cfor a time ranging between 4 and 15 h. After the completionreaction, the mixture was cooled and poured in ice-coldwater and stirred for 30 min, and then filtered and washedwell with water and dried. The compounds were purified byrecrystallization from either ethyl acetate. 2-Chloro-3-formyl-6-mthylquinoline (6b)It was obtained as a yellow powder. Yield: 92%; 1H-NMR(400 MHz, DMSO-d6) δ 10.36 (s, 1H), 8.83 (s, 1H), 8.00 (t,J = 1.4 Hz, 1H), 7.92 (d, J = 8.6 Hz, 1H), 7.82 (dd, J = 8.6,2.0 Hz, 1H), 2.55-2.49 (m, 3H); 13C-NMR (101MHz,DMSO-d6) δ 189.88, 148.54, 147.66, 141.03, 138.56,136.44, 129.13, 127.96, 126.77, 21.51. |
90% | With cetyltrimethylammonim bromide; trichlorophosphate In acetonitrile for 0.75h; Heating; |
87% | With trichlorophosphate at 90℃; for 10h; Cooling with ice; | 2 2) 3.5 ml of DMF and 17 ml of POCl3 were mixed under ice-cooling,After stirring, 2.24 g (15 mmol) of compound 1 was added, and the resulting solution was placed in a reflux apparatus,Heated to 90 ° C for 10 hours, cooled and poured into 500 ml of ice water, and the compound 2(2.7 g, yield 87%). |
87% | With trichlorophosphate at 90℃; for 10h; Cooling with ice; | 2 2) 3.5 ml DMF and 17 ml POCl3 are mixed under ice bath, then add 2.24g (15mmol) compound 1, the resulting solution is placed in reflux device, heating to 90 °C reflux for 10 hours, after cooling is poured into 500 ml ice water, filtered to obtain compound 2 (2.7g, yield 87%). |
85% | With trichlorophosphate In 1,2-dichloro-ethane at 40℃; for 1h; ultrasound irradiation; | |
85% | With trichlorophosphate at 85℃; for 24h; | |
84.83% | With bis(trichloromethyl) carbonate In chloroform at -5 - 51℃; for 6.5h; Green chemistry; | 4 Example 4 This example provides a process for the synthesis of 2-chloro-3-formyl-6-methylquinoline with the following main steps: under ice-salt bath, 3.00g (20.13 mmol) acetanilide, 8.03 g (27.04 mmol) of BTC and 10 mL of trichloromethane 4.2 mL (54.66mmol) DMF was added dropwise over 80 min after the temperature was maintained below -5 °C. The rate of the bubble overflow was controlled by the tail gas uptake rate. After the addition of the DMF, the mixture was stirred continuously for 10 min. For water bath, plus Heat to 51 °C, reaction 5 hours, steaming part of the solvent, adding ice water, 10% NaOH to adjust the pH to 8 ~ 9, pumping, recrystallization. The yield was 84.83%. |
83% | With trichlorophosphate at 75℃; for 8h; | 4.2. General procedure for the synthesis of compounds 2a-2f General procedure: POCl3 (9.0 mL, 96 mmol) was added dropwise to DMF (2.8 mL,36 mmol) precooled at 0 C. Followed by adding acetanilide(10 mmol), the mixture was heated to 75 °C and stirred at thattemperature for 8 h. After been cooled to room temperature, themixture was poured to 100mL of ice-water. The precipitate wasobtained by suction filtration, washed with cold water and dried toafford the product.1H NMR and 13C NMR data of selected productsare shown as follows. |
82% | Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 5℃; Stage #2: 4-Methylacetanilide at 75 - 80℃; for 8h; Stage #3: With water Cooling with ice; | |
80% | With trichlorophosphate at 80 - 90℃; for 16h; | |
80% | With trichlorophosphate at 80 - 90℃; | |
80% | Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 5℃; for 1h; Stage #2: 4-Methylacetanilide at 0 - 80℃; Inert atmosphere; | 1.1 General procedure for synthesis of 2-chloroquinoline-3-carbaldehydes (13-18) General procedure: A round bottom flask charged with N, N-dimethylformamide (7.0 mol) was placed on an ice bath and the temperature kept at 0-5 °C. To this flask, phosphorus oxychloride (12.0 mol) was added dropwise and the reaction mixture was stirred for 1 h at 0-5 °C. The appropriate N-phenylacetamide (1.0 mol) was then added and stirred for a further 30 min followed by heating under reflux for 5-4 h under N2 atmosphere. After the reaction was completed (TLC monitoring), the mixture was poured into 200 g of crushed ice under constant stirring. The precipitate obtained was vacuum filtered, washed with water (2 × 30 mL), air-dried and recrystallised from EtOAc to give the relevant compounds in 36-84% yields. |
80% | Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 5℃; for 1h; Inert atmosphere; Stage #2: 4-Methylacetanilide at 0℃; Inert atmosphere; Reflux; | |
77% | With trichlorophosphate at 0 - 65℃; for 8h; | General procedure for the synthesis of substituted quinoline carbaldehyde (1a-b) General procedure: At 0 °C to a stirred solution of POCl3 (39.6 g, 259 mmol) and anhydrous DMF (8 g, 111mmol) was added acetanilide (5 g, 37 mmol). The mixture was then heated to 65 °C and the progress of the reaction was monitored by TLC analysis. After 8 h the reaction mixturewas then cooled to room temperature and added cautiously into ice-cold water. The solid precipitated was collected by filtration to isolate the compound 1a as yellow solid. |
75% | Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: 4-Methylacetanilide Reflux; | |
74% | With trichlorophosphate at 85℃; for 2.25h; | |
74% | With trichlorophosphate at 75 - 80℃; | |
73% | With trichlorophosphate at 0 - 20℃; for 0.25h; Microwave irradiation; | |
72% | With trichlorophosphate at 0℃; for 8h; | |
72% | Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 2h; Stage #2: 4-Methylacetanilide at 0℃; | |
70.7% | With trichlorophosphate at 75℃; for 10h; | |
70% | Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: 4-Methylacetanilide for 16.0833h; Reflux; | |
66.7% | With trichlorophosphate at 0 - 85℃; | 4.2.2. 2-Chloro-6-methylquinoline-3-carbaldehyde (S3) POCl3 (111 mL, 1.19 mol) was added drop wise to DMF (40 mL, 0.51 mol) at 0 °C, followed by a portion wise addition of N-acetyl-p-toluidine (S2) (25.7 g, 0.17 mol). The resulting mixture was stirred for 30 min at rt and the reaction mixture heated at 85 °C for 6 h. The resulting solution was cooled to rt and slowly poured into ice-water. The resulting precipitate was filtered, washed with water, dried and crystallized from ethyl acetate to give aldehyde (S3) (23.6 g, 66.7%). 1H NMR (400 MHz, DMSO-d6 ppm): 2.48 (s, 3H), 7.79 (d, 1H), 7.91 (d, 1H), 8.01 (s, 1H), 8.81 (s, 1H), 10.35 (s, 1H). m/z (APCI+) 206 (M+H+). mp 124-125 °C. |
65% | With silica gel; trichlorophosphate for 0.0416667h; Microwave irradiation (300 W); | |
64% | Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: 4-Methylacetanilide at 70 - 80℃; for 16h; | |
64% | Stage #1: N,N-dimethyl-formamide With phosphorus pentachloride at 0℃; for 0.25h; Stage #2: 4-Methylacetanilide for 4h; Reflux; | Synthesis of 2-chloroquinoline-3-carbaldehydes 5a-i General procedure: Dimethylformamide (12 mmol, 3 equiv.) was cooled at 0°C in a round flask equipped with a drying tube and phosphorus pentachloride (18 mmol, 4.5 equiv.) was added slowly and the mixture was stirred for 15 minutes keeping the temperature below 0°C. To this solution was added in a portion the corresponding acetanilide (4 mmol, 1 equiv.) and the reaction mixture was heated under reflux and stirring for the appropiate time depending of the acetanilide. The resulted mixture was cooled to 0°C and the solution was poured slowly into ice-water and stirring for ten minutes, obtaining a yellow solid which was filtered, washed several time with cold water and dried under vacuum. The 2-chloroquinoline-3-carbaldehydes were recrystallized according to the literature. |
34% | Stage #1: N,N-dimethyl-formamide; 4-Methylacetanilide With trichlorophosphate at 0℃; Heating / reflux; Stage #2: With water; sodium carbonate at 0℃; | 103.2 Step 2: 2-Chloro-6-methylquinoline-3-carbaldehyde Phosphoryl trichloride (237.2 g, 1.55 mol) was added dropwise with stirring, while cooling to 0° C. to N,N-dimethylformamide (40.4 g, 552.74 mmol). N-p-Tolylacetamide (33 g, 221.19 mmol) was then added and the resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at reflux. The reaction mixture was then quenched by the adding 3000 ml of H2O/ice. Adjustment of the pH to 9 was accomplished by the addition of Na2CO3. The resulting solution was extracted with DCM (3*3000 mL). The organics were combined, dried over MgSO4, and concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by column chromatography on silica gel eluding with a 1:10 EtOAc:hexanes to afford 15.3 g (34%) of 2-chloro-6-methylquinoline-3-carbaldehyde as a yellow solid. LCMS: 206 (M+H)+. |
With trichlorophosphate | ||
With trichlorophosphate | ||
With trichlorophosphate | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate Stage #2: 4-Methylacetanilide Heating; Further stages.; | ||
With trichlorophosphate for 16h; Reflux; | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: 4-Methylacetanilide for 16h; Heating; | ||
With trichlorophosphate at 80 - 90℃; | ||
With trichlorophosphate | ||
With trichlorophosphate for 17h; Reflux; | ||
With bis(trichloromethyl) carbonate In dichloromethane | ||
With trichlorophosphate Heating; | ||
Stage #1: N,N-dimethyl-formamide; 4-Methylacetanilide With trichlorophosphate at 0 - 75℃; Inert atmosphere; Stage #2: With water at 0 - 10℃; for 0.5h; Inert atmosphere; | ||
With trichlorophosphate at 80℃; | ||
With trichlorophosphate | ||
With trichlorophosphate at 80 - 90℃; | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 5℃; for 0.0833333h; Stage #2: 4-Methylacetanilide at 75 - 80℃; for 8h; | Synthesis of Quinoline 2a-d General procedure: POCl3 (9 ml, 98.28 mmol) was added drop wise to DMF (2.7 ml, 34.65 mmol) whilst maintaining the temperature at 0-5°C. The mixture was allowed to stir for about 5 min. Acetanilide 1a (10.37 mmol) was then added and the resulting solution heated for 8 h at 75-80°C. The reaction mixture was cooled to room temperature and then poured into crushed ice with stirring. A pale yellow precipitate appeared immediately and was filtered and washed with water and then dried. The crude compound was recrystallized from ethyl acetate. | |
With trichlorophosphate at 0 - 5℃; | ||
With trichlorophosphate at 0 - 75℃; for 6h; | ||
With trichlorophosphate | ||
With trichlorophosphate at 90℃; for 16h; | General procedure for the preparation of compounds 2-4 General procedure: The mixture of compound 1 (15 mmol), DMF (5 mL) and POCl3 (17 mL) was refluxed at 90 C for 16 h. After the reaction, the mixture was poured into ice water and then filtered to offer pale powder of compound 2. Compound 2 (10 mmol) was treated with 70% acetic acid aqueous solution (200 mL) at 95 C for 10 h and then the solution was cooled to room temperature to offer needle crystals of compound 3. The mixture of compound 3 (1 mmol), ethanol (50 mL) and different primarily amines (1.1 mmol) or hydraziniums (1.0 mmol) was blended together and reacted at 80 C for 10 h. After cooling to room temperature, powders or crystals of compound 4 were obtained. | |
With trichlorophosphate | ||
at 80℃; | ||
With trichlorophosphate at 85℃; for 18h; | ||
With trichlorophosphate | ||
With trichlorophosphate at 85 - 90℃; Reflux; | Synthesis of 2-chloroquinoline-3-carbaldehyde (4a) [44-55] General procedure: Synthesis of 2-chloroquinoline-3-carbaldehyde (4a) [44-55] To a stirred solution of N-phenylacetamide(3a) (5 mmoles) in dry DMF (15 mmoles), POCl3 (60 mmoles) was added drop-wise. The mixture was refluxed for overnight on water bath at 85-90 °C. The reaction mixture was quenched with crushed ice present in a 500 mL beaker and stirred well for some time. The precipitate obtained was filtered, dried and purified by recrystallization processby using ethyl acetate to afford pure compound 4a in 82% yield. Similarly, the other aldehydes 4b-c were prepared by using the procedures reported earlier. | |
With trichlorophosphate at 80℃; for 18h; | Synthesis of 2-chloroquinoline-3-carbaldehydes 15a-e General procedure: These compounds were prepared by an adaptation of the Meth-Cohn method (see ref 4 in article). N,N-Dimethylformamide (9.1 g, 9.6 mL, 0.125 mol) was cooled to 0 °C and phosphoryl chloride (53.7 g, 32.2 mL, 0.35 mol) was added dropwise with stirring. To this solution the corresponding acetanilide 14 (0.05 mol) was added and the temperature of the reaction mixture was raised to 80 °C during 18 h. The cooled reaction mixture was poured into ice-water (300 mL) and stirred for 1h at 0-10 °C. The precipitate formed corresponding to 2-chloro-3-quinolinecarbaldehyde 15 was filtered off, washed with water (100 mL), dried, and recrystallized from ethyl acetate. | |
With trichlorophosphate for 16h; Reflux; | ||
With trichlorophosphate at 75℃; for 4h; | ||
With trichlorophosphate at 90℃; | Scheme-I: Synthetic route of 2-oxo-quinoline-3-carbaldehyde schiff-base derivatives. Reagents and conditions: (a) DMF/POCl3, 90 °C; (b) 70 % acetic acidaqueous solution, 95 °C; (c) R2-NH2, ethanol, 80 °C | |
With trichlorophosphate | ||
With trichlorophosphate at 80℃; | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate Stage #2: 4-Methylacetanilide | ||
With trichlorophosphate Heating; | ||
With trichlorophosphate at 80℃; | ||
With trichlorophosphate at 0 - 90℃; | General procedure for synthesis of 2-chloro-3-formylquinolines 1a-g General procedure: To a solution of acetanilide (5 mmol) in dry dimethylformamide (DMF) (20 mmol) at 0-5 °C with stirring, POCl3 (35 mmol) was added dropwise, and the mixture was stirred at 80-90 °C for time ranging between 8 and 16 h. The mixture was poured into crushed ice and stirred for 5 min, and the resulting solid was filtered and washed well with water and dried. The compounds were subjected to silica gel column chromatography. | |
With trichlorophosphate at 0℃; Reflux; | General procedure for the synthesis of 6-substituted-2-chloroquinoline-3-carbaldehydes 2a-d (Meth-Cohnet al., 1981) General procedure: Dimethylformamide 9.6 mL (0.125 mol)was cooled to 0 C, and phosphoryl chloride 32.2 mL(0.35 mol) was added drop-wise with stirring. To thissolution was added substituted acetanilide 1a-d (0.05 mol)and the reaction mixture was refluxed for 16-17 h. Reactioncompletion was monitored by TLC. The reactionmixture was poured into ice water (300 mL) and stirred for30 min at 0-10 °C. The resulting suspension was filteredand washed with water to give the intermediates 2a-d. | |
With trichlorophosphate at 100℃; for 16h; | ||
With trichlorophosphate at 100℃; for 16h; | ||
With trichlorophosphate | ||
With trichlorophosphate at 80℃; | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: 4-Methylacetanilide at 80℃; | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: 4-Methylacetanilide at 80℃; for 18h; | ||
With trichlorophosphate at 90℃; | ||
With trichlorophosphate at 0 - 82℃; for 24h; Inert atmosphere; | ||
With trichlorophosphate | ||
With trichlorophosphate at 85℃; for 12h; | ||
With trichlorophosphate for 16h; Reflux; | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 5℃; Stage #2: 4-Methylacetanilide at 80 - 90℃; | ||
With trichlorophosphate for 24h; Heating; | ||
Stage #1: N,N-dimethyl-formamide; 4-Methylacetanilide With trichlorophosphate Stage #2: Heating; | ||
With trichlorophosphate at 80 - 90℃; | ||
With trichlorophosphate at 0℃; Reflux; | ||
With trichlorophosphate at 70℃; for 18h; | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 5℃; for 0.333333h; Stage #2: 4-Methylacetanilide at 80 - 90℃; for 18h; | 2-Chloro-3-formylquinolines (1a and 1b). General procedure: A modified method of Meth-Cohn et al. 39 was used. Briefly, freshly dried DMF (33.5 mmol) was transferred to a dry round bottomed flask fitted with a condenser attached to a drying tube. POCl3 (93.8 mmol) was added dropwise to the DMF at 0-5 °C for 10-15 min. After addition, the reaction was stirred for 20 min and the acetanilide (13.4 mmol) added. The reaction was stirred at 80-90 °C for12-16 h. On completion, the reaction mixture was cooled to room temperature and poured in ice water. A golden yellow precipitate was filtered and recrystallized in ethyl acetate. | |
With trichlorophosphate at 0 - 90℃; for 18h; | 5.1.2 General procedure for preparation of chloroquinoline-3-carbaldehydes (3a-i) General procedure: Phosphorus oxychloride (16.3mL, 175mmol) was added dropwise with continuous stirring over 15min to DMF (5.8mL, 62.5mmol) at 0°C, then appropriate anilides 2a-i (25mmol) was added portionwise. The reaction mixture was heated at water bath at 70-90°C with stirring for 18h. The mixture was poured onto crushed ice and stirred well. After being awhile the obtained precipitate was filtered, dried and purified by crystallization using ethyl acetate to afford pure light yellow products in 60-87% yield [54-60]. | |
With trichlorophosphate at 70 - 90℃; for 18h; | ||
With trichlorophosphate at 70 - 80℃; for 16h; | Preparation of 2-chloroquinolin-3-carbaldehyde (6c-i) General procedure: Vilsmeir-Haack adduct was prepared by adding phosphorous oxychloride (0.35 mol) drop wise to the cold solution of DMF (0.125 mol) with constant stirring. To this adduct, substituted acetanilide (0.05 mol) was added slowly and stirred well for 15-20 min. The mixture was then refluxed for 16 h at 70-80°C. After completion of the reaction, the contents were poured into ice water and stirred for 30 min. The 2-chloroquinoline-3-carbaldehyde 6c-i precipitated out was filtered and washed well with water. Dried and recrystallized from ethyl acetate. | |
With trichlorophosphate at 70 - 90℃; for 18h; | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.25h; Stage #2: 4-Methylacetanilide at 80℃; for 8h; | ||
With trichlorophosphate at 70 - 80℃; | ||
With trichlorophosphate at 0 - 80℃; | 1. Preparation of 2-chloroquinoline-3-carbaldehydes 3(a,b) General procedure: 2-Chloroquinoline-3-carbaldehydes 3(a,b) were prepared by using method reported by Meth-Cohn and coworkers [1]. POCl3 (65.3 mL, 107.45 g, 0.70 mol) was added drop-wise to DMF (19.3 mL, 18.26 g, 0.25 mol) with constant stirring while maintaining the temperature of the flask at 0 °C. To the resulting Vilsmeyer reagent, acetanilide 2 (0.10 mol) was added and the reaction mixture was heated at 70-80 °C. The progress of the reaction was monitored thin layer chromatography (TLC). The reaction mixture was then poured on crushed ice (500 g) cautiously and stirred vigorously at 0-10 °C. The precipitated 2-chloroquinoline-3-carbaldehyde 3 was filtered, washed with excess water, dried, and recrystallized from ethyl acetate. | |
With trichlorophosphate for 6h; Reflux; | ||
With trichlorophosphate at 0℃; Reflux; Heating; | 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. | |
With trichlorophosphate at 0 - 90℃; | General procedure for the synthesis of 6-substituted-2-chloro-3-formyl quinolines, 2 General procedure: To a solution of substituted acetanilide (5 mmol) indry dimethyl formamide (15 mmol) at 0-5°C withstirring POCl3 (60 mmol) was added drop-wise andthe mixture stirred at 80-90°C for time rangingbetween 4-16 h. The product obtained was pouredinto crushed ice, stirred for 5 min and the resultingsolid mass was filtered, washed well with water anddried. The compounds were recrystallized from ethylacetate. | |
With trichlorophosphate at 0 - 80℃; | 3.3. Preparation of 2-Chloroquinoline-3-carbaldehydes 3a-f General procedure: A Vilsmeier reagent, prepared from dropwise addition of POCl3 (65.3 mL, 0.70 mol)to DMF (19.3 mL, 0.25 mol) at 0 C with continuous stirring, was added correspondingacetanilide 2a-f (0.10 mol). The resulting mixture was heated to 80 C for 6-18 h. Afterthe completion of the reaction (monitored by TLC), the reaction mixture was cautiouslypoured onto crushed ice (500 g) and stirred for 30 minutes at 0-10 C. The precipitated solidwas filtered off, washed with excess water, dried, and recrystallized from ethyl acetate toproduce 2-chloroquinoline-3-carbaldehydes 3a-f [55]. | |
With trichlorophosphate at 0 - 90℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With O-trifluorobenzenesulfonyl-acetohydroxamic acid ethyl ester; toluene-4-sulfonic acid In water; acetonitrile at 20℃; Inert atmosphere; | 1 Example 3 General procedure: Table 2 shows the results of examining various catalysts in the reaction of synthesizing N- (2-naphthyl) acetamide from 2-acetonaphthone. Examples of the acid catalyst include hydrochloric acid, sulfuric acid, methanesulfonic acid, tosylic acid monohydrate, trifluoromethanesulfonic acid, bistrifluoromethanesulfonimide, boron trifluoride diethyl ether complex, scandium (III) trifluoromethanesulfonate, trifluoromethanesulfone Iron (III) oxide, trifluoromethanesulfoCopper (II) trifluoromethanesulfonate, bismuth trifluoromethanesulfonate (III), titanium tetrachloride and iron trichloride have excellent effects (Entries 2 to 14). |
95% | With zinc(II) chloride; hydroxylamine-O-sulfonic acid In water at 20℃; for 3h; | Secondary Amides from Ketones; General Procedure General procedure: To a stirring solution of ZnCl2 (0.05 mmol, 10 mol%) in H2O (2 mL) at r.t. in an open round-bottom flask, ketone 1 (0.5 mmol, 1.0 equiv) wasadded, followed by HOSA (1.5 equiv). The reaction mixture was stirred at the indicated temperature and for the duration indicated in Scheme 2. After completion, the reaction mixture was diluted with EtOAc (15 mL) and washed with sat. aq Na2CO3 (3 × 5 mL). The organic layer was washed with brine (5 mL) and dried over anhydrous Na2SO4.The crude product obtained after removal of all volatiles in vacuo was washed with n-hexane to remove some minor nonpolar impurities. |
94% | With XY-zeolite; hydroxylamine hydrochloride for 0.0333333h; microwave irradiation; |
93% | With sodium hydrogen sulfate; hydroxylamine hydrochloride; silica gel for 0.0416667h; Heating; | |
93% | With O-benzenesulfonyl-acetohydroxamic acid ethyl ester; toluene-4-sulfonic acid In water; acetonitrile at 23℃; for 24h; Inert atmosphere; | |
92% | With alumina sulfuric acid; hydroxylamine hydrochloride at 150℃; for 3.5h; | |
91% | With hydroxylamine hydrochloride at 160℃; for 0.0333333h; microwave irradiation; | |
91% | With sodium azide; sulfuric acid; silica gel at 60℃; for 0.416667h; | |
90% | With mesitylenesulfonylhydroxylamine In acetonitrile at 20℃; for 6h; | General procedure for the preparation of amides from ketones General procedure: To a round bottom flask, equipped with a magnetic stirring bar, was added ketone 1 (0.5 mmol, 1.0 equiv.) and acetonitrile (2 mL) at room temperature. To this stirred solution, freshly prepared O-(Mesitylsulfonyl)hydroxylamine 2 (2.0 equiv.) was added. The reaction mixture was stirred for the specified duration and temperature. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with ethyl acetate (10 mL) and washed with a saturated aqueous NaHCO3 solution (3 x 5 mL). The combined organic layer was washed with brine solution and dried over anhydrous Na2SO4. Solvent was removed under reduced pressure to get the crude product. The reaction that required elevated temperature was stirred first at room temperature for 2 hours after addition of MSH and then heated at 70 °C for the specified time. |
87% | With methanesulfonic acid; tetrabutylammoniun azide In 1,2-dimethoxyethane at 80℃; for 0.0833333h; Flow reactor; | |
85% | With hydroxylamine hydrochloride; zinc(II) oxide at 140℃; for 1h; | |
85% | With hydroxylamine hydrochloride at 150℃; for 1h; | |
85% | With phosphorus pentaoxide; sodium azide; silica gel for 0.166667h; microwave irradiation; | |
85% | With cesiumhydroxide monohydrate; copper(II) bis(trifluoromethanesulfonate); hydroxylamine-O-sulfonic acid In dichloromethane; 2,2,2-trifluoroethanol at 70℃; for 16h; | Amides from Ketones General procedure: To a stirred solution of Cu(OTf)2 (0.05 mmol, 10 mol%) in TFE/CH2Cl2 (1:4, 2-3 mL) were added ketone (0.5 mmol, 1.0 equiv), HOSA (2.0 equiv), and CsOH·H2O (2.0 equiv) at rt. The reaction mixture was maintained at the temperature and for the time indicated in Scheme 2. After completion, the mixture was diluted with CH2Cl2 (10 mL) and washed with sat. aq Na2CO3 (3 × 5 mL). The combined organic layers were washed with brine (5 mL) and dried (anhyd Na2SO4). The crude product obtained after removal of all volatiles in vacuo was purified by SiO2 (100-200 mesh) chromatography using EtOAc/hexane as eluent. |
80% | With trifluorormethanesulfonic acid; hydroxylamine hydrochloride In formic acid for 7h; Heating; | |
80% | With hydroxylamine hydrochloride; water; Thiamine hydrochloride In 1,4-dioxane at 90℃; for 0.666667h; | Experimental procedure for the synthesis of amides using thiamine hydrochloride as a catalyst General procedure: A mixture of ketone 1 (2 mM), hydroxylamine hydrochloride (3 mM) and thiamine hydrochloride (0.4 mM) was taken in 10mL dioxane:H2O (9:1) in a round-bottom flask and heated at 90 °C for specific time (30-90 min). The progress of the reaction was monitored using thin layer chromatography (tlc). After completion of the reaction, the reaction flask was cooled to room temperature. The residue was taken in ethyl acetate (30 ml), washed with water (2x15 ml), brine (1x15 ml) and the organic layer was dried (anhyd. Na2SO4). The resulting ethyl acetate solution was concentrated and the desired amides 2 (75-95% yield) are obtained by recrystallization from ethanol. |
79% | With hydroxylamine hydrochloride; oxalic acid at 110℃; for 11.5h; | |
78% | With nitromethane; sulfuric acid In formic acid at 80 - 120℃; | 3 e): Take a reaction tube and add 35-45mg (0.3mmol) of p-methylacetophenone, 0.5mL of nitromethane, 60-100mg (0.6mmol) of 98% concentrated sulfuric acid, 30-60mg (0.75mmol) of formic acid, Stir at 80-120°C for 1-72 hours. After the completion of the reaction, 10 mL of sodium hydroxide solution was added to quench the reaction, extracted with ethyl acetate 3 times, the organic phase was washed with 5 mL of brine, and the organic phases were combined and separated by column chromatography to obtain 35 mg of p-methylacetanilide with a yield of 78%. |
70% | With hydroxylamine hydrochloride In acetonitrile Reflux; | 2.4. Synthesis of amides General procedure: Ketones (1 mmol) and hydroxylamine hydrochloride (0.0694g,1 mmol) were dissolved in CH3CN (10 mL) and stirred for 10 - 15 min. The complex (CS-SalBr-Zn-L) (10 mol%) were added tothe reaction flask. The reaction mixture was heated under reflux for specific time (3e7 h). After completion, the reaction mixture was cooled to room temperature and the catalyst was removed by filtration. The filtrate was treated with ethyl acetate (3 10 mL).The combined organic layers were treated with saturated brine solution and dried over anhydrous sodium sulphate. The removal of solvent yields crude product, which after purification by column chromatography over Silica gel (100e200 mesh), afforded the desired products. |
70% | With formic acid; nitromethane; trifluoromethylsulfonic anhydride In acetic acid at 100℃; for 12h; | |
7.98% | With Mexican Bentonite; hydroxylamine hydrochloride for 0.25h; Irradiation; | |
With hydroxylamine hydrochloride; trifluoroacetic acid at 70℃; for 16h; Inert atmosphere; | General procedure: In a typical experiment a glass reactor equipped with magneticbar was charge with 1.5 mmol of the selected ketone or aldehyde,4.4 mmol of hydroxylamine hydrochloride and 22 mmol oftrifluoroacetic acid under inert atmosphere of nitrogen. The reactiontime was computed after the heating fluid starts to circulate in the reactor jacket. The reaction mixture was heated at 70 °C for 16 h, andthen cooled down.Products were isolated after distillation of the TFA (at 40 °C and250 Pa of pressure) and in a rotary evaporator, washed with coldwater and recrystallized from hexane or light petroleum ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | With Selectfluor; sodium chloride; In water; for 24.0h;Reflux; | 1a as example: To a stirred suspension of N-(p-tolyl)acetamide 1a (75 mg, 0.5 mmol) and Selectfluor (213 mg, 0.6 mmol) in water (3.0 mL) was added HBr (40% aqueous, 0.08 mL, 0.55 mmol), and the mixture was stirred for 5 min at room temperature. After 1a was consumed, as indicated by TLC, the reaction mixture was quenched with saturated aqueous Na2S2O3 (2.0 mL) and water (20.0 mL), and extracted with CH2Cl2 (10.0 mL) three times. The residue obtained after evaporation of the solvent was purified by column chromatography on silica gel (petroleum ether-ethyl acetate = 6:1, v/v) to afford N-(2-bromo-4-methylphenyl)acetamide 2a as a white solid (108 mg, 95% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 4-Methylacetanilide With phenylsilane-d3; C36H48F6N6NiO5S2 In toluene at 110℃; for 24h; Inert atmosphere; Schlenk technique; Stage #2: With hydrogenchloride | |
91% | With C18H32ClIrO2P2; tris(pentafluorophenyl)borate; hydrogen; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate In toluene at 120℃; for 24h; chemoselective reaction; | |
90% | With borane-ammonia complex; boron trifluoride diethyl ether complex; tris(pentafluorophenyl)borate In 1,2-dichloro-ethane at 60℃; for 24h; |
90% | With (Ru(1,2:5,6-η-1,5-cyclooctadiene)(η(3)-methallyl)2); formic acid; bis(trifluoromethanesulfonyl)amide; triethylamine; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine] In dibutyl ether at 130℃; for 24h; | |
74% | With C20H25Cl2CoN3; sodium triethylborohydride In 1,2-dimethoxyethane at 100℃; for 6h; Inert atmosphere; | 8 Example 8: Reduction of 4-methylacetanilide to N-ethyl-p-toluidine: Under an inert atmosphere, the substrate 4-methylacetanilide (149 mg, 1 mmol), polymethylhydrosiloxane (668 μL, 3 mmol), Co-2 catalyst (9.0 mg, 0.02 mmol), Sodium triethylborohydride (40 μL, 0.04 mmol) and ethylene glycol dimethyl ether (2 mL), and the resulting mixture was stirred well.The reaction was carried out in an oil bath at 100°C for 6 hours, the reaction system was cooled to room temperature, ethyl acetate and saturated KF aqueous solution were added to dilute and quench, the layers were separated, the organic phase was taken, dried, concentrated, and the crude product was subjected to flash silica gel column chromatography to obtain 100 mg of light yellow final product. Oily liquid, yield: 74%. |
With lithium aluminium hydride In diethyl ether | ||
With dimethylsulfide borane complex In tetrahydrofuran at 90℃; for 0.333333h; Inert atmosphere; Flow reactor; chemoselective reaction; | ||
65 %Chromat. | With cobalt(II) bis[bis((trifluoromethyl)sulfonyl)amide]; trimethylsilyl trifluoropmethanesulfonate; (p-anisyl)triphos; hydrogen In n-heptane at 125℃; for 14h; Autoclave; Sealed tube; | |
Stage #1: 4-Methylacetanilide With dimethylbis(η5-pentamethylcyclopentadienyl)thorium; 4,4,5,5-tetramethyl-1,3,2-dioxaborolane In hexadeuterobenzene at 70℃; Inert atmosphere; Sealed tube; Stage #2: With mesoporous silica at 60℃; for 8h; Inert atmosphere; | ||
With dimethylsulfide borane complex In tetrahydrofuran at 60℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With 1,3-Diiodo-5,5-dimethyl-2,4-imidazolidinedione; 4,4'-dimethoxyphenyl disulfide In acetonitrile at 20℃; for 13h; regioselective reaction; | |
88% | With N-iodo-succinimide; palladium diacetate; toluene-4-sulfonic acid In neat (no solvent, solid phase) at 20℃; for 3h; Milling; Sealed tube; regioselective reaction; | General procedure for synthesis of 2 General procedure: A mixture of acetanilide 1 (0.4 mmol), NIS (90.0 mg, 0.4 mmol), Pd(OAc)2 (9.0 mg, 0.04 mmol), and PTSA (152.0 mg, 0.8 mmol) was added to a 3 mL stainless-steel jar with a stainless-steel ball of 5 mm diameter. The vessel was sealed and vibrated in a Spex SamplePrep 8000 Mixer Mill at a frequency of 875 cycles per minute at room temperature for 3 h. The same reaction was repeated again. Then, the reaction mixtures from two runs were washed with acetone and collected into a round-bottomed flask together with silica gel and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel (ethyl acetate/petroleum ether = 1:3) to afford the corresponding product 2. |
82% | With N-iodo-succinimide; bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; <i>N</i>-<i>tert</i>-butoxycarbonyl-<i>L</i>-phenylalanine; silver(I) triflimide In 1,2-dichloro-ethane at 20℃; for 2h; Inert atmosphere; Sealed tube; |
79% | With N-iodo-succinimide; cobalt acetylacetonate; trifluoroacetic acid; silver(l) oxide In 1,2-dichloro-ethane at 60℃; for 16h; regioselective reaction; | |
76% | With N,N,N-trimethylbenzenemethanaminium dichloroiodate; zinc(II) chloride In acetic acid at 70℃; for 24h; | |
40% | With sodium tungstate; sulfuric acid; dihydrogen peroxide; acetic acid; potassium iodide at 50℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With cerium(III) chloride heptahydrate; N-fluorobis(benzenesulfon)imide In acetonitrile at 100℃; for 0.166667h; Sealed tube; Microwave irradiation; | 4. Screening of other Lewis acids NFSI (9.5 mg, 0.03 mmol) and the Lewis acid (0.002 mmol) were added to a solution of the oxime 1 (30 mg, 0.2 mmol) in CH3CN (0.2 mL). Then the solution was irradiated under microwaves at 100 °C for 10 min. The solvent was removed in vacuo and the crude mixture was purified by a flash column chromatography on silica gel to afford the product 2. |
97% | at 120℃; for 1.5h; Heating; | |
97% | With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; zinc(II) chloride In acetonitrile for 1h; Heating; |
96% | With 2,2-dichloro-1,3-dicyclohexylimidazolidine-4,5-dione In acetonitrile at 80℃; for 0.25h; Inert atmosphere; Schlenk technique; | |
94% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In tetrahydrofuran; ethyl acetate at 70℃; for 2h; Inert atmosphere; | 20 T3P catalyzed synthesis of amides/lactams from ketoximes: To a solution of ketoxime (0.01 mol) in THF (10 mL) was added T3P (15 mol %, 50% soln in EtOAc) and the resulting reaction mixture was stirred at reflux for 1-4 h under nitrogen atmosphere. When the reaction was completed as confirmed by TLC, the solvent was removed under vacuum and the residue was diluted with water (20 mL). The product was extracted with ethyl acetate (2 × 20 mL) and the combined organic phase was washed with saturated NaHCO3 solution (1 × 10 mL) and brine. The organic phase was dried over anhydrous Na2SO4. The solvent was removed under reduced pressure to afford the desired amides in good purity. |
93% | In acetonitrile at 80℃; for 8h; | |
91% | With phthalic anhydride; zinc trifluoromethanesulfonate In acetonitrile at 20℃; for 6h; Inert atmosphere; | 3. General procedure for o-phthalic anhydride/Zn(OTf)2 co-catalyzed Beckmann rearrangement General procedure: Oxime 1 (1.0 mmol, 1.0 equiv), Zn(OTf)2 (73.7 mg, 0.2 mmol, 0.2 equiv) and o-phthalic anhydride (15.0 mg, 0.1 mmol, 0.1 equiv) were dissolved in 1.0 mL CH3CN at rt under nitrogen atomesphere and stirred until the complete consumption of the oxime monitored by TLC analysis. The mixture was evaporated and the residue was purified on flash column chromatography with petroleum ether/ethyl acetate (5:1~2:1) as eluent to afford the desired amide 2. |
79% | With 1,1,1,3',3',3'-hexafluoro-propanol; tetrabutylammonium tetrafluoroborate; water In 1,2-dichloro-ethane at 20℃; for 0.733333h; Electrochemical reaction; | |
72% | With S4N4*SbCl5 In toluene at 60℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With copper diacetate; oxygen; toluene-4-sulfonic acid In acetic acid; toluene at 60℃; for 16h; | |
85% | With palladium diacetate; toluene-4-sulfonic acid; p-benzoquinone In acetic acid; toluene at 20℃; | |
82% | With palladium 10% on activated carbon; oxygen; toluene-4-sulfonic acid; p-benzoquinone at 85℃; for 3.33333h; Flow reactor; Green chemistry; regioselective reaction; |
79% | With oxygen In toluene at 80℃; for 16h; | |
78% | With palladium 10% on activated carbon; p-benzoquinone at 85℃; for 24h; | |
55% | With potassium hexafluorophosphate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; copper(II) acetate monohydrate In water at 120℃; for 20h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium phosphate; copper(l) iodide; glycine In 1,4-dioxane at 100℃; for 24h; | |
91% | With [Cu8(H){S2P(OiPr)2}6](PF6); caesium carbonate In N,N-dimethyl-formamide at 120℃; for 24h; | |
90% | With aluminum oxide; potassium fluoride; copper(l) iodide; 1,10-Phenanthroline In toluene at 110℃; for 6h; |
90% | With aluminum oxide; potassium fluoride; copper(l) iodide; N,N'-Dibenzylethylenediamine In toluene at 110℃; for 2h; Inert atmosphere; | |
82% | With 2-Phenyl-1,3,2-dioxaborinane In 1,4-dioxane at 115℃; for 30h; Inert atmosphere; | |
81% | With copper(I) thiophene-2-carboxylate; sodium t-butanolate In dimethyl sulfoxide at 100℃; for 6h; Inert atmosphere; | |
75% | With copper(ll) sulfate pentahydrate; sodium ascorbate; sodium t-butanolate In dimethyl sulfoxide at 100℃; for 7h; | 1 General procedure for N-arylation of primary amides General procedure: CuSO4*5H2O (0.15 mmol), NaAsc (0.3 mmol), aryl iodides (1mmol), primary amides (1.2mmol), t-BuONa (2.0 mmol), and DMSO (3mL) were added to a flask. The reaction mixture was stirred under air, and then cooled to room temperature and extracted with ethyl acetate (3×10 mL). The organic layer was then dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The secondary amides were finally obtained by column chromatography on silica gel eluted with ethyl acetate/petroleum ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: polyphosphoric acid / 5 h / 160 °C 2: phosphorus oxychloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium phosphate In <i>tert</i>-butyl alcohol at 110℃; for 12h; | |
81% | With copper(I) oxide; potassium phosphate; N<SUP>1</SUP>,N<SUP>2</SUP>-bis(thiophen-2-ylmethyl)oxalamide In <i>tert</i>-butyl alcohol at 130℃; for 24h; Schlenk technique; | |
74% | Stage #1: acetamide; para-chlorotoluene With copper(l) iodide; potassium carbonate; trans-N,N'-dimethylcyclohexane-1,2-diamine In acetonitrile for 0.00277778h; Inert atmosphere; Glovebox; Stage #2: In acetonitrile at 200℃; for 1h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: <i>p</i>-toluidine With tetrafluoroboric acid In water Inert atmosphere; Stage #2: acetonitrile With potassium phosphate; water at 80℃; for 12h; | General procedure General procedure: A mixture of aryl diazonium tetrafluoroborates compounds (0.5 mmol), nitriles (0.5 mmol), H2O (1.5 mmol) and K3PO4 (0.6 mmol) was dissolved in acetonitrile (1.0 mL) or ethyl acetate (1.0 mL) under N2 atmosphere, stirred at 80 oC for 12h. Removal of the solvent under a reduced pressure gave the crude product; pure product was obtained by passing the crude product through a short silica gel column using Hexane/EtOAc (1:1-2:1) as eluent. |
83% | With tert.-butylnitrite; trifluorormethanesulfonic acid; water at 60℃; for 24h; | 2. General procedure for the synthesis of acetamide General procedure: To a stirred solution of amine (1.0 mmol) in CH3CN (5.0 mL) was addedt-BuONO (1.5 mmol, 1.5 equiv), CF3SO3H (1.5 mmol, 1.5 equiv) and H2O (5.0 mmol,5.0 equiv). The reaction mixture was stirred under an atmosphere of air at 60 oC for24 h. After the reaction was complete, the reaction mixture was purified by flashchromatography on silica gel with a mixture of petroleum ether and ethyl acetate aseluent. |
74% | With tert.-butylnitrite; tetrabutylammomium bromide; water; toluene-4-sulfonic acid at 60℃; for 23h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium fluoride; palladium diacetate In 1,2-dichloro-ethane at 90℃; for 11h; | |
71% | With palladium diacetate at 80℃; | |
65% | With (dibenzoyloxyiodo)benzene In 2-methyltetrahydrofuran at 25℃; for 8h; regioselective reaction; | 4.1 4.2. General procedure for the oxidative benzylic CH amidation of 4-methylanilides (1) General procedure: To a solution of 4-methylanilide (1) (0.20 mmol) in 2-methyltetrahydrofuran (2.0 mL) was added the N-fluorobenzenesulfonimide (126 mg, 0.40 mmol). The reaction was stirred at 25 °C for 8 h under air. Then the mixture was poured into water (25 mL) and extracted with ethyl acetate (3 * 15 mL). The combined organic layer was dried (Na2SO4) and filtered over Celite, evaporated in vacuo. The residue was purified by column chromatography (ethyl acetate/hexane) to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 83% 2: 7% | With acetylhydroxamic acid; sulfuric acid In acetonitrile at 80℃; for 0.216667h; Microwave irradiation; | Typical procedure for the preparation of amide under microwave heating: General procedure: Acetophenone 1a (1.0 g, 8.3 mmol), acetohydroxamic acid (0.92 g, 12.5 mmol), acetonitrile (3 ml), and conc. H2SO4 (0.2 ml) were taken into a 10 ml pressure tube and subjected to microwave heating (CEM discover, 360 W, 80 °C, 25 psi) for 10 min. The crude product obtained was purified as mentioned above to afford acetanilide 2a (0.94 g, 86%) and it gave spectral data same as above. |
1: 68% 2: 19% | With hydroxylamine hydrochloride In acetonitrile at 70℃; for 15h; | |
With hydroxylamine hydrochloride In acetonitrile at 70 - 110℃; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium hydroxide In N,N-dimethyl-formamide at 20℃; | |
90% | With sodium hydroxide In N,N-dimethyl-formamide at 20℃; | Take the synthesis of 1a2 as an example: Referring to the above reaction formula, p-toluidine (1.607 g, 15.0 mmol) and CH 2 Cl 2 (50.0 mL) were sequentially added to a 100 mL round bottom flask equipped with a magnetic stir bar.And Et3N (4.170 mL, 30.0 mmol), and finally acetyl chloride (1.273 mL, 18.0 mmol).The reaction mixture was stirred at room temperature with a magnetic stirrer.After TLC showed the consumption of p-toluidine was completed, the reaction was quenched with saturated NaHCO3 (100 mL).It was then extracted 3 times with CH 2 Cl 2 (100.0 mL).The combined organic phases were washed twice with brine (50 mL).The solid obtained by distilling off the organic solvent was washed with a mixture of petroleum ether/ethyl acetate (5:1, by volume).The white solid p-methylacetanilide (2.104 g, 94% yield) was obtained. Add to a stirred solution of p-methylacetanilide (1.492 g, 10.0 mmol) and NaOH (600 mg, 15.0 mmol) in DMF (30 mL)2-Methyl-3-bromopropene (1.311 mL, 13.0 mmol), and the resulting mixture was stirred at room temperature with a magnetic stirrer.After TLC showed the consumption of p-methylacetanilide, the reaction was quenched with brine (60 mL) and extracted three times with CH2Cl2 (100.0 mL).The residue obtained by evaporating the organic solvent was subjected to column chromatography on silica gel ( petroleum ether-ethyl acetate = 20:1, volume ratio).N-(2-methylallyl)-N-p-tolylacetamide 1a2 (1.830 g, 90% yield) was obtained as a colourless oil. |
90% | With sodium hydroxide In N,N-dimethyl-formamide at 20℃; | 1 Procedure: To a 100 mL round bottom flask equipped with a magnetic stirrer, p-toluidine (1.607 g, 15.0 mmol) and CH 2 Cl 2 (50.0 mL) were sequentially added.And Et3N (4.170mL, 30.0mmol), finally added acetyl chloride(1.273 mL, 18.0 mmol).The reaction mixture was stirred at room temperature with a magnetic stirrer.After TLC showed that the raw material was consumed by p-toluidine,The reaction was quenched with saturated NaHCO3 (100 mL).It was then extracted 3 times with CH 2 Cl 2 (100.0 mL).The combined organic phases were washed twice with brine (50 mL).Evaporation of the organic solvent to obtain a solid petroleum ether / ethyl acetate (5:1, by volume)The mixture was washed to give a white solid, p-methylacetanilide (2.104 g, 94% yield). To a stirred stirred p-methylacetanilide (1.492 g, 10.0 mmol) and NaOH (600 mg, 15.0 mmol) in DMF (30 mL)2-Methyl-3-bromopropene (1.311 mL, 13.0 mmol) was added to the solution.The resulting mixture was stirred with a magnetic stirrer at room temperature.TLC shows that after the consumption of p-methylacetanilide is completed,The reaction was quenched with brine (60 mL) andEtOAcEtOAcThe residue obtained by evaporating the organic solvent was subjected to column chromatography on silica gel ( petroleum ether-ethyl acetate = 20:1, volume ratio).N-(2-methylallyl)-N-p-tolylacetamide 1a2 (1.830 g, 90% yield) was obtained as a colourless oil. |
Stage #1: 4-Methylacetanilide With sodium hydride In tetrahydrofuran at 20℃; for 0.333333h; Stage #2: 2-methyl-3-bromo-1-propene In tetrahydrofuran at 70℃; for 2h; | ||
1.83 g | With sodium hydroxide In N,N-dimethyl-formamide at 20℃; | 1 Add a p-toluidine to a 100 mL round bottom flask with a magnetic stir bar.(1.607 g, 15.0 mmol), CH2Cl2 (50.0 mL), and Et3N (4.170 mL, 30.0 mmol), and finally acetyl chloride (1.273 mL, 18.0 mmol).The reaction mixture was stirred at room temperature with a magnetic stirrer. TLC shows the starting material p-toluidineAfter the completion of consumption, the reaction was quenched with saturated NaHCO3 (100 mL) and then extracted three times with CH2Cl2 (100.0 mL). The combined organic phases were washed twice with brine (50 mL). The solid obtained by evaporation of the organic solvent was washed with a mixture of petroleum ether/ethyl acetate (5:1, vol.) to give a white solid p-methylacetanilide (2.104 g, 94% yield).To keep stirring2-A solution of acetanilide (1.492 g, 10.0 mmol) and NaOH (600 mg, 15.0 mmol) in DMF (30 mL)Base-3-bromopropene (1.311 mL, 13.0 mmol), and the resulting mixture was stirred at room temperature with a magnetic stirrer. TLC displayAfter the consumption of p-methylacetanilide was completed, the reaction was quenched with brine (60 mL) and extracted three times with CH2Cl2 (100.0 mL).The residue obtained by evaporation of the organic solvent was subjected to column chromatography ( petroleum ether - ethyl acetate = 20:1, volume ratio).Colorless oil N-(2-methylallyl)-N-p-tolylacetamide 1a2 (1.830 g, 90% yield). |
With sodium hydroxide In N,N-dimethyl-formamide at 20℃; | ||
With sodium hydroxide In N,N-dimethyl-formamide at 20℃; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With trichlorophosphate In toluene at 90 - 100℃; for 3h; | Procedure B (for amidines 2, 5, 6, 7) General procedure: To the solution of 0.50 g (2.0 mmol) amine and 2.5 mmol of appropriate amides in 5 ml toluene, the phosphorus oxychloride (0.2 ml, 2.1 mmol) was added dropwise under stirring. The resulting mixture was heated for 3 h at 90-100 °C. After cooling to the ambient temperature, toluene evaporated in vacuum and the mixture was neutralized by 50 ml of 2% NaOH water solution, the crude product was filtered, washed with water, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With tert.-butylhydroperoxide; palladium diacetate In water at 95℃; for 12h; | 2. General procedures General procedure: A mixture of anilide (1, 1.0 mmol), Pd(OAc)2 (0.20 mmol, 20 mol%) in toluene (2, 3 mL) was stirred at 95 °C and tert-butyl hydroperoxide (THBP, 12-16 equiv, 70% solution in water) was injected in an hour. The reaction system was stirred for 12h. After the reaction, the mixture was concentrated. The residue was purified by flash chromatography on silica gel (eluant: petroleum ether/ethyl acetate ) to afford the diaryl ketone 3. |
77% | With tert.-butylhydroperoxide; palladium diacetate In dimethyl sulfoxide at 100℃; for 20h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sodium azide; C16H17AuBrN3O; water; trifluoroacetic acid In 1,2-dichloro-ethane at 25℃; for 2h; Schlenk technique; Inert atmosphere; regioselective reaction; | 6.3. General procedure for catalysis General procedure: Alkynes (0.5 mmol), NaN3 (1 mmol), H2O (1 mmol), catalyst 1(2 mol%) and TFA/DCE (2 mL, 1:1 v/v) were taken in a Schlenk tube inside a fume hood. The reaction mixture was allowed to stir for 2 h at room temperature. Then 25 mL water was added to it and theorganics were extracted with ethyl acetate (3 x 10 mL). The solventwas evaporated under reduced pressure. The residue was purifiedby column chromatography on silica gel (petroleum ether/ethylacetate) to give the desired amide product. Yields were calculatedbased on isolated products. GC yields were reported in presence ofinternal standard dodecane. |
76% | With trimethylsilylazide; silver carbonate; trifluoroacetic acid In water; 1,2-dichloro-ethane at 60℃; for 12h; Schlenk technique; Inert atmosphere; | |
70% | With formic acid; nitromethane; trifluoromethylsulfonic anhydride In acetic acid at 100℃; for 12h; |
52% | With (triphenylphosphine)gold(I) chloride; trimethylsilylazide; water; silver carbonate; trifluoroacetic acid In 1,2-dichloro-ethane at 60℃; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With dihydrogen peroxide In water at 25℃; for 8h; Green chemistry; | |
93% | With 2,2'-azobis(isobutyronitrile); oxygen In acetonitrile at 80℃; for 24h; Sealed tube; | 4 General procedure for AIBN-promoted oxidative formation of amides from amines and 1, 3-diketones (3a) General procedure: A sealed tube was equipped with a magnetic stir bar was charged with 1,3-di-ketone 1a (0.075 g, 0.75 mmol), aniline 2a (0.0232 g, 0.25 mmol), AIBN (0.0164 g, 0.0001 mmol), and acetonitrile (1.0 mL). The above reaction mixture was stirred at 80°C under O2 atmosphere for 24 h. After completion of the reaction, the reaction was then cooled to room temperature, mixture was diluted with ethyl acetate. After removal of the solvent under reduced pressure the left out residue was purified by column chromatography using silica gel with hexane and ethyl acetate as eluent to get 3a in 82% yield (0.0278 g). The spectral data was well matched with reported values. The above procedure is followed for the synthesis of all products reported in this manuscript. |
85% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium t-butanolate In toluene at 100℃; for 16h; |
81.4% | With iodine; toluene-4-sulfonic acid In 1,4-dioxane at 140℃; for 36h; Schlenk technique; | General procedure: A mixture of amine 1 (0.50 mmol), 1,3-diketone 2 (0.60 mmol, 1.2 equiv), iodine(12.7 mg, 0.05 mmol, 10 mol%) and TsOHH2O (19.0 mg, 0.10 mmol, 20 mol%) in 1,4-dioxane (3 mL) was added into a Schlenk flask (25 mL) and stirred at room temperature.The mixture was stirred at 140 C until the reaction was finished. Then, the solvent wasevaporated under reduced pressure and the residue was purified by column chromatography(petroleum ether/ethyl acetate 5:1 to 2:1) to afford the product 3. N-(p-tolyl)acetamide (3aa): Yield: 71%, 53.2 mg, white solid, mp 145-147 °C. 1H NMR (600 MHz, d6-DMSO) δ 9.85 (s, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 2.23 (s, 3H), 2.03 (s, 3H); 13C NMR (151 MHz, d6-DMSO) δ 168.5, 137.3, 132.3, 129.5, 119.4, 24.4, 20.9; HRMS Calcd for C9H11NONa: 172.0738 [M+Na]+; found: 172.0741. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With silver hexafluoroantimonate; (p-cymene)ruthenium(II) chloride; copper(II) bis(trifluoromethanesulfonate); silver(l) oxide In N,N-dimethyl-formamide at 110℃; for 20h; Inert atmosphere; Sealed tube; | |
79% | With silver hexafluoroantimonate; (p-cymene)ruthenium(II) chloride; copper(II) bis(trifluoromethanesulfonate); silver(l) oxide In N,N-dimethyl-formamide at 110℃; for 20h; Inert atmosphere; Sealed tube; | 6 N-(5-methyl-[1,1'-biphenyl]-2-yl)acetamide In a baffled, closable reactor vessel, a mixture comprising N-(p-tolyl)acetamide (149 mg, 1.0 mmol), [{RuC12 (p-isopropyltoluene)} 2] (30.6 mg, 5.0 MoS%), AgSbF6 (68.7 mg, 0.2 mmol), Ag20 (232 mg, 1.0 mmol Mol), Cu (OTf) 2 (72.3 mg, 0.2 mmol) and phenylboronic acid (183 mg, 1.5 mmol) in anhydrous DMF (3.0 mL) was stirred at 110 & lt; 0 & gt; C under a nitrogen atmosphere Stir for 20 hours. The reaction mixture was then treated with EtOAc (75 mL) at room temperature Diluted with water and filtered through celite and silica gel, and the filtrate was concentrated. Will be so obtained The crude product was purified by chromatography on silica gel (n-hexane / EtOAc: 7/3). To give 178 mg of N - (5-methyl- [l, r-biphenyl] -2-yl) acetamide as colorless solid On the value of 79%). |
73% | With silver hexafluoroantimonate; [RhCl2(p-cymene)]2; copper(II) bis(trifluoromethanesulfonate); silver(l) oxide In tetrahydrofuran at 110℃; for 20h; Inert atmosphere; Glovebox; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With carbon monoxide; palladium diacetate In acetonitrile at 60℃; | 4.5 General procedure for the synthesis of acetanilides from guanidines General procedure: To a screw-cap reaction tube was added symmetrical N,N′-disubstituted guanidines 1a (0.2 mmol), Pd(OAc)2 (5 mol%, 2.2 mg), Cu(OAc)2 (0.2 mmol, 36.3 mg). The reaction tube was evacuated and back-filled with CO (three times, balloon). MeCN (2mL) was added using a syringe and the mixture was heated to the desired temperature with use of an oil bath. When the reaction was completed (detected by TLC), the mixture was cooled to room temperature and vented to discharge the excess CO. The solvent was concentrated by evaporation in vacuo. The residue was purified by flash column chromatography on silica gel to afford the desired product amides 2a with petroleum ether/ethyl acetate as the eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With water; benzoic acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone; iron(II) chloride In 1,2-dichloro-ethane at 60℃; for 24h; Schlenk technique; Inert atmosphere; | N-Phenylpropionamide (2a); Typical Procedure General procedure: To a Schlenk tube (25 mL) were added sequentially FeCl2 (6.3 mg, 0.05 mmol), DDQ (136 mg, 0.6 mmol), PhCOOH (305 mg, 2.5 mmol), (1-azidopropyl)benzene (1a) (80.5 mg, 0.5 mmol), H2O (18 μL, 1.0 mmol) and dry DCE (2 mL). The resulting mixture was stirred at 60 °C under an argon atmosphere for 24 h. The mixture was filtered, concentrated and purified by flash chromatography on silica gel (PE-EtOAc, 10:1) to afford amide 2a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With tetrabutylammonium tetrafluoroborate In ethyl acetate at 20℃; for 24h; Electrochemical reaction; | |
93% | With tris(2,2'-bipyridyl)ruthenium dichloride In acetonitrile at 20℃; Irradiation; | |
80% | With copper(II) acetate monohydrate In acetonitrile at 80℃; for 18h; Sealed tube; | Typical procedure for acetylation of phenols and anilines General procedure: Under air atmosphere, anilines or phenols (0.5 mmol), potassium thioacetate (3.0 eq.),Cu(OAc)2H2O (0.2 eq.), MeCN (3 mL) were added to a screw-capped vial. Thereaction vial was placed in a temperature-controlled oil bath pot set at 80 °C. Thereaction progress was monitored by TLC. After the completion of the reaction, thevial was removed from the oil bath pot and was left to cool to the ambient temperature.The solution was filtered though a short column of silica gel and washed with EtOAc.The filtrate was concentrated under reduced pressure to leave a crude product, whichwas purified by flash column chromatography on silica gel with Petroleumether/EtOAc as an eluent to give the desired product. |
80% | With tert.-butylnitrite In acetonitrile at 25℃; for 4h; | 2 Example 2: Synthesis of 4-methylacetanilide Add 2 mL of acetonitrile, 32.1 mg of p-toluidine, 68.4 mg of potassium thioacetate, and 6.2 mg of tert-butyl nitrite to a 25 mL reaction tube, and react with magnetic stirring at 25° C. for 4 hours. After the reaction is over, extract with ethyl acetate, combine the organic phases, evaporate most of the solvent under reduced pressure, and perform column chromatography on the remaining mixture with petroleum ether and ethyl acetate combined with a 10:1 composition as the eluent After separation and purification, the desired product is obtained as a light yellow solid, 35.8 mg, with a yield of 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With potassium carbonate In water at 80℃; for 1.66667h; Green chemistry; | 4.2.1 General procedure for the acylation of aromaticand aliphatic amines General procedure: A mixture of the acylating reagents 1a-e (0.5 mmol), arylamine (1.5 mmol), or alkyl amine (0.75 mmol) and K2CO3(2 mmol for aromatic amines and 1 mmol for aliphaticamines) was stirred in H2O (1-2 mL) at 80 °C for the appropriateperiod of time. After completion of the reactionas indicated by TLC, the reaction mixture was acidifiedwith 5 % HCl and extracted with EtOAc (50 mL) and water(10 mL). The combined organic layer was concentratedin vacuo and purified by column chromatography onsilica gel to afford the pure product (compounds 2a-p and3a-q). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With silver(I) acetate; palladium diacetate; In trifluoroacetic acid; at 120℃; for 24h;Sealed tube; Inert atmosphere; Schlenk technique; | General procedure: A seal-tube (15 mL) initially fitted with a septum containing anilide 1 (0.5 mmol), Pd(OAc)2 (11.3 mg, 0.05 mmol, 10 mol%), and AgOAc (83.5 mg, 0.5 mmol) was evacuated and purged with N2 three times. TFA (4.0 mL), and ethyl 2-iodoacetate (2a; 160 mg, 0.75 mmol) were added to the system and the reaction mixture was stirred at 120 C for 24 h. The mixture was cooled to r.t. and filtered through a short Celite pad and washed with CH2Cl2 several times. The filtrate was concentrated under vacuum and purified on a silica gel column using hexane/EtOAc as eluent to give the corresponding pure oxindole product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With silver(I) acetate; palladium diacetate; trifluoroacetic acid; at 120℃; for 24h;Sealed tube; Inert atmosphere; Schlenk technique; | General procedure: A seal-tube (15 mL) initially fitted with a septum containing anilide 1 (0.5 mmol), Pd(OAc)2 (11.3 mg, 0.05 mmol, 10 mol%), and AgOAc (83.5 mg, 0.5 mmol) was evacuated and purged with N2 three times. TFA (4.0 mL), and ethyl 2-iodoacetate (2a; 160 mg, 0.75 mmol) were added to the system and the reaction mixture was stirred at 120 C for 24 h. The mixture was cooled to r.t. and filtered through a short Celite pad and washed with CH2Cl2 several times. The filtrate was concentrated under vacuum and purified on a silica gel column using hexane/EtOAc as eluent to give the corresponding pure oxindole product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With C18H32ClIrO2P2; tris(pentafluorophenyl)borate; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; deuterium In toluene at 120℃; for 24h; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tert.-butylhydroperoxide; iodine In water at 80℃; for 24h; | Typical procedure: N-phenylbenzamide (Table 2, entry 1) General procedure: A mixture of N-phenylacetamide(2a, 135 mg, 1.0 mmol), iodine (254 mg, 1 mmol), TBHP (387 mg, 3.0 mmol, 70% in water) and toluene (2.0 mL) was added successively in a round-bottom flask, and the resulting soln. stirred for 24 h at 80 °C. The mixture was then subjected to purification by preparative thin-layer chromatography (PE-EtOAc, 10:3) to afford product 3aa. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.3% | With N-iodo-succinimide; palladium on activated charcoal In tetrahydrofuran at 50℃; for 5h; | 1 In 50 ml of the magneton with stirring, of the reflux condensation tube of three-mouth flask is added in the amines of the formula shown in the acetyl-substrate (R is hydrogen or 4 bit chlorine or methyl, or 3 bits of the methoxy or ethoxy, or 2 position of the ethyl), in order to R group is 4 bit methyl for example, adding the raw materials 4 -methyl acetanilide 0.75g (5.0mmol), palladium/carbon 0.53g (to palladium, 0.50mmol, specifications and purity: 10% on dry carbon support, purchased from lark prestige technology Company), N-iodo succinimide 2.25g (10.0mmol), adding tetrahydrofuran 20 ml as solvent, under air atmosphere heated to 50 degree c reaction 5 hours. After the reaction, filtration and recovery of palladium/carbon, reduced pressure distillation to remove the solvent, the residue for column chromatography purification (silica gel: 200 - 300 mesh; mobile phase, petroleum ether: ethyl acetate=1:1, v/v) to obtain white solid target product, the obtained product is 2-iodo-4-methyl acetanilide 1.27g, yield is 92.3%. |
62% | With hydrogen fluoride; antimony pentafluoride; sodium iodide at -20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With tert.-butylhydroperoxide In water; chlorobenzene at 80℃; for 2h; | Methyl N-phenyloxamate (2a); Typical Procedure General procedure: In a round-bottomed flask, a mixture of dimethyl 2-(phenylamino)maleate (1a; 0.094 g, 0.4 mmol), 70% aq TBHP (0.131 g, 1mmol), and PhCl (1 mL) was heated in an oil bath at 80 °C for 2h. When the reaction was complete (TLC), the mixture wascooled to r.t. and the reaction was quenched with sat. aq Na2SO3(1 mL). The mixture was extracted with EtOAc, and the organicphase was dried (Na2SO4), filtered, and concentrated underreduced pressure. The residue was purified by column chromatography[silica gel, hexane-EtOAc (8:1)] to give a white solid;yield: 0.063 g (88%); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With N-Bromosuccinimide; palladium diacetate; toluene-4-sulfonic acid In neat (no solvent, solid phase) at 20℃; for 3h; Milling; Sealed tube; regioselective reaction; | General procedure for synthesis of 2 General procedure: A mixture of acetanilide 1 (0.4 mmol), NIS (90.0 mg, 0.4 mmol), Pd(OAc)2 (9.0 mg, 0.04 mmol), and PTSA (152.0 mg, 0.8 mmol) was added to a 3 mL stainless-steel jar with a stainless-steel ball of 5 mm diameter. The vessel was sealed and vibrated in a Spex SamplePrep 8000 Mixer Mill at a frequency of 875 cycles per minute at room temperature for 3 h. The same reaction was repeated again. Then, the reaction mixtures from two runs were washed with acetone and collected into a round-bottomed flask together with silica gel and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel (ethyl acetate/petroleum ether = 1:3) to afford the corresponding product 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With trichlorophosphate In toluene at 90 - 100℃; for 3h; | Procedure B (for dyes 4, 6, 7): General procedure: To the solution of 0.50 g (2.0 mmol) amine and 2.5 mmol of appropriateamides in 5 ml toluene, the phosphorus oxychloride (0.2 ml,2.1 mmol) was added dropwise under stirring. The resulting mixturewas heated for 3 h at 90-100 °C. After cooling to the ambient temperature,toluene evaporated in vacuum and the mixture neutralized by50 ml of 2% NaOH water solution, the crude product was filtered,washed with water, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In lithium hydroxide monohydrate at 20℃; for 12h; | 2 Example 2 4-methylaniline (0.3 mmol), thioacetic acid (0.45 mmol), and water solvent (H2O) (1 mL) were successively added to the reaction tube at room temperature under air atmosphere, followed by reaction at room temperature for 12 hours, and the reaction ended The product was isolated by post-column chromatography in 99% yield. |
93% | With 9-mesityl-10-methylacridin-10-ium tetrafluoroborate In acetonitrile at 20℃; for 5h; Irradiation; | |
93% | With 9-mesityl-10-methylacridin-10-ium tetrafluoroborate In acetonitrile at 20℃; for 5h; Irradiation; | 2 Example 2: Preparation of N- (p-tolyl) acetamide (3b) In air, p-methylaniline (0.2 mmol, 22 mg) was dissolved in acetonitrile (2 mL), and Mes-Acr-MeBF4 (2 mol%, 2 mg) and thioacetic acid (0.4 mmol, 30 mg) were added. The mixture was stirred for 5 hours at room temperature under a 36W blue LED. The mixture was quenched with water (2 mL) and then extracted with EtOAc (3 x 4 mL). The organic phase was washed with brine, dried over Na 2 SO 4 and spin-dried, and then separated by column chromatography to obtain 28 mg of a white solid product with a yield of 93%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Stage #1: 4-methylethylbenzene With N-hydroxyphthalimide; oxygen; cobalt(II) diacetate tetrahydrate In acetic acid at 80℃; for 12h; Stage #2: With formic acid; nitromethane; trifluoromethylsulfonic anhydride In acetic acid at 100℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With iron(III) chloride In 1,2-dichloro-ethane at 120℃; for 24h; Sealed tube; Green chemistry; | 2.1. General procedure for the synthesis of products 3 General procedure: N-methoxy amide 1 (0.2 mmol), arylboronic acid 2 (0.3 mmol),FeCl3 (20 mmol%) and dichloroethane (DCE, 2.0 mL) were added to asealed tube. Then the mixture was stirred at 120 C in the air for 24 h. After the disappearance of substrate as indicated by TLC, the mixturewas concentrated in vacuo and the resulting crude product was purifiedby column chromatography to afford the products 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium peroxodisulfate; methanesulfonic acid; NiCl2·6H2O In 1,2-dichloro-ethane at 140℃; for 24h; Sealed tube; | Thiolated Compounds 3 and 4; General Procedure General procedure: A reaction vessel (micro vial, 10 mL) was charged with an anilide 1 (0.2 mmol, 1.0 equiv), a thiol 2 (0.4 mmol, 2.0 equiv), NiCl2·6H2O (0.04 mmol, 20 mol%), K2S2O8 (0.4 mmol, 2.0 equiv), CH3SO3H (0.1 mmol, 0.5 equiv), and DCE (1.5 mL). The reaction vessel was sealed and the contents were stirred at 140 °C for 24 h. After cooling to r.t., the reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (3 × 10 mL). The combined extracts were washed with aq NaHCO3 and dried (Na2SO4). After evaporation of the solvent, the crude product was purified by column chromatography on silica gel (PE/EtOAc 6:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium peroxodisulfate; methanesulfonic acid; NiCl2·6H2O In 1,2-dichloro-ethane at 140℃; for 24h; Sealed tube; | Thiolated Compounds 3 and 4; General Procedure General procedure: A reaction vessel (micro vial, 10 mL) was charged with an anilide 1 (0.2 mmol, 1.0 equiv), a thiol 2 (0.4 mmol, 2.0 equiv), NiCl2·6H2O (0.04 mmol, 20 mol%), K2S2O8 (0.4 mmol, 2.0 equiv), CH3SO3H (0.1 mmol, 0.5 equiv), and DCE (1.5 mL). The reaction vessel was sealed and the contents were stirred at 140 °C for 24 h. After cooling to r.t., the reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (3 × 10 mL). The combined extracts were washed with aq NaHCO3 and dried (Na2SO4). After evaporation of the solvent, the crude product was purified by column chromatography on silica gel (PE/EtOAc 6:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With potassium peroxodisulfate; methanesulfonic acid; NiCl2·6H2O In 1,2-dichloro-ethane at 140℃; for 24h; Sealed tube; | Thiolated Compounds 3 and 4; General Procedure General procedure: A reaction vessel (micro vial, 10 mL) was charged with an anilide 1 (0.2 mmol, 1.0 equiv), a thiol 2 (0.4 mmol, 2.0 equiv), NiCl2·6H2O (0.04 mmol, 20 mol%), K2S2O8 (0.4 mmol, 2.0 equiv), CH3SO3H (0.1 mmol, 0.5 equiv), and DCE (1.5 mL). The reaction vessel was sealed and the contents were stirred at 140 °C for 24 h. After cooling to r.t., the reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (3 × 10 mL). The combined extracts were washed with aq NaHCO3 and dried (Na2SO4). After evaporation of the solvent, the crude product was purified by column chromatography on silica gel (PE/EtOAc 6:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With potassium peroxodisulfate; methanesulfonic acid; NiCl2·6H2O In 1,2-dichloro-ethane at 140℃; for 24h; Sealed tube; | Thiolated Compounds 3 and 4; General Procedure General procedure: A reaction vessel (micro vial, 10 mL) was charged with an anilide 1 (0.2 mmol, 1.0 equiv), a thiol 2 (0.4 mmol, 2.0 equiv), NiCl2·6H2O (0.04 mmol, 20 mol%), K2S2O8 (0.4 mmol, 2.0 equiv), CH3SO3H (0.1 mmol, 0.5 equiv), and DCE (1.5 mL). The reaction vessel was sealed and the contents were stirred at 140 °C for 24 h. After cooling to r.t., the reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (3 × 10 mL). The combined extracts were washed with aq NaHCO3 and dried (Na2SO4). After evaporation of the solvent, the crude product was purified by column chromatography on silica gel (PE/EtOAc 6:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With potassium peroxodisulfate; methanesulfonic acid; NiCl2·6H2O In 1,2-dichloro-ethane at 140℃; for 24h; Sealed tube; | Thiolated Compounds 3 and 4; General Procedure General procedure: A reaction vessel (micro vial, 10 mL) was charged with an anilide 1 (0.2 mmol, 1.0 equiv), a thiol 2 (0.4 mmol, 2.0 equiv), NiCl2·6H2O (0.04 mmol, 20 mol%), K2S2O8 (0.4 mmol, 2.0 equiv), CH3SO3H (0.1 mmol, 0.5 equiv), and DCE (1.5 mL). The reaction vessel was sealed and the contents were stirred at 140 °C for 24 h. After cooling to r.t., the reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (3 × 10 mL). The combined extracts were washed with aq NaHCO3 and dried (Na2SO4). After evaporation of the solvent, the crude product was purified by column chromatography on silica gel (PE/EtOAc 6:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With potassium peroxodisulfate; methanesulfonic acid; NiCl2·6H2O In 1,2-dichloro-ethane at 140℃; for 24h; Sealed tube; | Thiolated Compounds 3 and 4; General Procedure General procedure: A reaction vessel (micro vial, 10 mL) was charged with an anilide 1 (0.2 mmol, 1.0 equiv), a thiol 2 (0.4 mmol, 2.0 equiv), NiCl2·6H2O (0.04 mmol, 20 mol%), K2S2O8 (0.4 mmol, 2.0 equiv), CH3SO3H (0.1 mmol, 0.5 equiv), and DCE (1.5 mL). The reaction vessel was sealed and the contents were stirred at 140 °C for 24 h. After cooling to r.t., the reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (3 × 10 mL). The combined extracts were washed with aq NaHCO3 and dried (Na2SO4). After evaporation of the solvent, the crude product was purified by column chromatography on silica gel (PE/EtOAc 6:1). |
Tags: 103-89-9 synthesis path| 103-89-9 SDS| 103-89-9 COA| 103-89-9 purity| 103-89-9 application| 103-89-9 NMR| 103-89-9 COA| 103-89-9 structure
[ 25027-73-0 ]
N-(4-(Aminomethyl)phenyl)acetamide hydrochloride
Similarity: 0.91
[ 16375-88-5 ]
N-(4-(Hydroxymethyl)phenyl)acetamide
Similarity: 0.87
[ 25027-73-0 ]
N-(4-(Aminomethyl)phenyl)acetamide hydrochloride
Similarity: 0.91
[ 16375-88-5 ]
N-(4-(Hydroxymethyl)phenyl)acetamide
Similarity: 0.87
[ 25027-73-0 ]
N-(4-(Aminomethyl)phenyl)acetamide hydrochloride
Similarity: 0.91
[ 16375-88-5 ]
N-(4-(Hydroxymethyl)phenyl)acetamide
Similarity: 0.87
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