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CAS No. : | 539-03-7 | MDL No. : | MFCD00000612 |
Formula : | C8H8ClNO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | GGUOCFNAWIODMF-UHFFFAOYSA-N |
M.W : | 169.61 | Pubchem ID : | 10871 |
Synonyms : |
4-Chloroacetanilide
|
Signal Word: | Warning | Class: | |
Precautionary Statements: | P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
100% | In dichloromethane at 20℃; Inert atmosphere; | |
99% | In chloroform | |
98% | With aluminum(III) oxide at 25℃; for 0.0833333h; |
98% | With cadmium(II) oxide at 80℃; for 0.166667h; Neat (no solvent); Microwave irradiation; | |
98% | at 20℃; for 0.5h; | Synthetic Procedures for N-acetylation of Amines General procedure: 0.0025 Moles of the respective amine was added to DES and stirred at different temperatures(depending on the solvent) until dissolved. 0.005 Moles of acetic anhydride wasadded to the mixture and stirred until the completion of reaction, which was monitoredby TLC. Upon completion, water was added to the reaction mixture; separated solid was filtered off and dried. DES was recycled by evaporation of water. Water soluble acetylatedamines were extracted with a suitable organic solvent. |
97% | With polyvinylpolypyrrolidone supported triflic acid In neat (no solvent) at 20℃; for 0.05h; Green chemistry; | General experimental procedure General procedure: To a mixture of substrate (1.0 mmol) and acetic anhydride (1.0 mmol), 0.008 g PVPP.OTf (3.4 mol%) was added. The mixture was stirred at room temperature for the time indicated in Tables 2, 3 and 4. The progress of the reaction was followed by TLC or GC for aliphatic alcohols. After completion of the reaction, ethyl acetate (2 9 10 cm3) was added, and the catalyst was separated by filtration. The filtrate was washed with an aqueous solution of NaHCO3 (10%, 2 9 10 cm3) and water (2 9 10 cm3) and dried with Na2SO4. The solvent was evaporated under reduced pressure to afford the expected product. |
97% | In dichloromethane at 20℃; for 0.25h; | 3.1. N-Phenylacetamide (11a) General procedure: To aniline (7a, 930mg, 10mmol) dissolved in DCM (10ml), acetic anhydride (1122mg, 11mmol) was added while cooling. After addition the reaction mixture was stirred at room temperature for 15 min. After completion of the reaction water was added and the compound was extracted using DCM. The solvent was evaporated under reduced pressure to afford compound 11a in excellent yield (98%). |
97% | With copper(II) ferrite In neat (no solvent) at 20℃; for 0.0833333h; Green chemistry; | |
96% | With potassium fluoride on basic alumina In toluene for 0.1h; | |
96% | With Co3O4 nanoparticles at 20℃; for 0.116667h; 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. |
96% | With Ni2B-Cu2O nanocomposite In neat (no solvent) at 40℃; for 0.0166667h; | 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. |
95% | With zinc oxide at 20℃; for 0.25h; | |
95% | With multi-walled carbonnanotubes functionalized with phosphonic acid In neat (no solvent) at 20℃; for 0.25h; | |
95% | 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 1,8-diazabicyclo[5.4.0]undec-7-en-8-ium acetate In neat (no solvent) at 50℃; for 0.5h; Green chemistry; | |
94% | With anhydrous Sodium acetate In water monomer for 0.166667h; Heating; | |
93% | at 20℃; | |
93% | In acetonitrile at 20℃; for 1h; | |
93% | With ZnAl2O4 nanoparticles at 20℃; for 0.0833333h; Neat (no solvent); | |
93% | With N,N'-dimethyl-N,N'-di(pyridin-4-yl)ferrocene-1,1'-dicarboxamide at 20℃; for 0.583333h; | |
93% | With silica-coated ferrite nanoparticles supported with montmorillonite-K10 at 20℃; for 0.333333h; | |
91% | With copper(II) bis(trifluoromethanesulfonate) In dichloromethane for 2h; Ambient temperature; | |
91% | In neat (no solvent) at 20℃; for 0.0833333h; Green chemistry; | |
91% | With [Ch-OSO3H]3W12PO40 at 20℃; for 0.7h; | 2 Example 2 10 mmol of p-chloroaniline, 25 mmol of acetic anhydride and 0.4 mmol of heterogeneous catalystWas 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).42min after the end of the reaction, filtration, filter residue with 5ml ethanol washing 3 times, collecting high-performance liquid chromatographic detection of chlorobenzeneThe conversion of the amine was 91% and the selectivity was 100%. The yield of N-acetyl-p-chloroaniline was calculated to be 91%.The washed residue was vacuum dried at 120 ° C and then recycled. |
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% | With pentaaminechlorocobalt(III) dichloride; phosphoric acid In neat (no solvent) at 75℃; for 0.166667h; Green chemistry; chemoselective reaction; | |
88% | With pentafluoroanilinium trifluoromethanesulfonate In neat (no solvent) at 20℃; for 0.166667h; | |
85% | With Mg-Al hydrotalcite with Mg/Al molar ratio in 2-3.5 In water monomer at 20℃; for 0.0833333h; | |
84% | With 7% w/w Pd/C In water monomer for 0.166667h; 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. |
83% | With polystyrene-nanoencapsulated FeCl3 catalyst In acetonitrile at 20℃; for 1h; | 2.3. A typical experimental procedure for the acetylation of alcohols, phenols, amines, and thiols with Ac 2 O catalyzed by PS-NC/ FeCl 3 General procedure: In a single-round bottomed flask (25 mL) containing a mixture of alcohol or phenol (1 mmol) and acetic anhydride (2 mmol) in CH 3 CN (4 mL) was added PS-NC/FeCl 3 (60 mg, 3.55 mol%, with respect to iron(III) content and the resulting heterogeneous mix- ture was stirred at room temperature for the time indicated in the Table ( 2 ). Upon completion of the reaction as monitored by TLC, the reaction mixture was filtered and the nanocapsules rinsed with CH 3 CN and methanol. The filtrate was washed with distilled water after quenching with a saturated solution of NaHCO 3 , dried over anhydrous MgSO 4 , and concentrated under reduced pressure us- ing a rotary evaporator to obtain the almost pure acetate products. It should be pointed out that the filtrate was analyzed at each run by ICP and atomic absorption spectroscopy to determine the leach- ing of the Fe(III) component. All products were characterized by a comparison of their spectral data (IR and 1 HNMR) and compared with the literature data. Nanoencapsulated catalyst recovery / reuse experiment, and determination of Fe in PS-NC / FeCl 3 by ICP analysis are given in ESI. |
82% | With supported L-pyrrolidine-2-carboxylic acid-4-hydrogen sulfate on Silica Gel at 20℃; for 1h; Green chemistry; | |
79% | In neat (no solvent) at 20℃; for 0.133333h; 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. |
75% | for 0.00277778h; Green chemistry; | General procedure for the synthesis of acetamides 3a-p,5a-d, and 7 General procedure: To a 10 mL round bottom flask was added 0.5 mmolof the amine and 0.1 mL of acetic anhydride. The reactionis instantaneous and exothermic, and after 10 s the solidproduct formed was filtered and washed with cold water.When no solid was immediately formed, 4 mL of coldwater was added, and the mixture allowed standing ina refrigerator for 24 h, leading to precipitation. To allsynthesized acetamides, measured physical data were inagreement to the reported values.17-19,27,31,32 |
55% | In dichloromethane at 20℃; Inert atmosphere; | |
51% | In dichloromethane at 20℃; Inert atmosphere; | |
With benzene | ||
With pyridine for 2h; Heating; | ||
With acetic acid Heating; | ||
In acetic acid for 0.25h; Heating; | ||
In water monomer | ||
With dmap; triethylamine In ethyl acetate at 22℃; for 17h; | ||
In dichloromethane | ||
In dichloromethane at 20℃; | ||
at 20℃; for 0.5h; | ||
With platinum nanoparticles supported on zirconia In methanol at 20℃; for 0.5h; | ||
With triethylamine In dichloromethane | ||
With dmap In dichloromethane at 0 - 20℃; Inert atmosphere; | ||
In dichloromethane at 20℃; for 1h; | ||
With acetic acid Reflux; | ||
In dichloromethane at 20℃; Inert atmosphere; | ||
With acetic acid | ||
With triethylamine In dichloromethane at 0 - 20℃; | ||
With acetic acid for 0.5h; Heating; | ||
With hydrogenchloride at 20℃; | ||
at 0 - 25℃; | ||
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; acetic acid | ||
With hydrogenchloride In water monomer | Step I Preparation of ortho substitutedacetanilide8, 9 General procedure: Aniline (5 ml) is dissolved in hydrochloricacid (4.6 ml concentrated hydrochloric acid and12.5ml water) in a beaker. To the clear solution are added acetic anhydride (6.5 ml).The mixture is stirreduntil acetic anhydride has completely reacted. Themixture are immediately poured in to a solution ofsodium acetate (8.3 gm) in water (25 ml).The solutionis stirred and cooled in ice. The separated acetanilideis fltered. It is recrystallized from boiling water(100-125 ml) to which ethyl alcohol has been added(Table 1). | |
In acetic acid for 1h; Reflux; | ||
In dichloromethane at 0 - 20℃; Inert atmosphere; | ||
In dichloromethane at 0 - 20℃; Inert atmosphere; | ||
With acetic acid for 1h; Reflux; | ||
at 20℃; for 3h; Inert atmosphere; | ||
In tetrahydrofuran at 20℃; | ||
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. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With indium; acetic acid In methanol at 20℃; for 2h; | |
89% | With samarium; acetic acid In methanol at 20℃; for 1.5h; | |
81% | Stage #1: 4-chlorobenzonitrile With trichlorosilane; triethylamine In acetonitrile at 0 - 25℃; for 1.5h; Stage #2: acetic anhydride With methanol In acetonitrile at 25℃; for 24h; chemoselective reaction; |
75% | With aluminum oxide; zinc In dichloromethane at 20℃; for 18h; | |
74% | Stage #1: 4-chlorobenzonitrile With sodium tetrahydroborate In water at 20℃; for 0.5h; Green chemistry; Stage #2: acetic anhydride In water at 20℃; for 2h; Green chemistry; | |
With tin(ll) chloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With Starbon-400-SO3H at 130℃; for 0.0333333h; Microwave irradiation; chemoselective reaction; | |
94% | With [((CH3)5Cp)2Zr(H2O)2OSO2C8F17]+[OSO2C8F17]-*THF In neat (no solvent) at 80℃; for 3h; | |
93% | With hydrazine hydrate for 5h; Heating; |
92% | With palladium (II) nanoparticles supported on Schiff-base modified clinoptilolite nanocatalyst In neat (no solvent) at 20℃; for 0.25h; 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. |
90% | With zinc(II) acetate dihydrate for 0.05h; Microwave irradiation; Sealed tube; chemoselective reaction; | |
90% | With aluminum oxide at 70℃; for 0.3h; Neat (no solvent); | |
90% | With magnatic matariel from fly ash In neat (no solvent) for 1h; Reflux; | |
88% | With ZnO nanofluid at 110℃; for 3h; neat (no solvent); | |
88% | With 1-methyl-3-(4-sulfonylbutyl)-1H-imidazol-3-ium trifluoromethanesulfonate at 90℃; for 0.166667h; 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. |
77% | for 0.333333h; microwave irradiation; | |
48% | at 150℃; microwave irradiation; | |
With trichlorophosphate | ||
unter Abdestillieren des Wassers; | ||
With thionyl chloride | ||
In dichloromethane for 0.5h; Inert atmosphere; | 2 2.2 Synthesis of 2,6-dibromo-4-chlorobenzenamine 1b Acetic acid (2 ml) was added to a stirred solution of 4-chlorobenzenamine (0.64 g, 5 mmol) in CH2Cl2. The solution was stirred for 30 min. After the solution cooled to 5 °C with ice bath, Br2 (2.00 g, 12.5 mmol) in 5 ml CH2Cl2 was slowly added to the stirred solution. The mixture was stirred for 5 h and neutralized by 10% saturated aqueous sodium hydroxide solution. The mixture was extracted three times with 50 ml petroleum ether. The combined organic phase was dried over MgSO4, filtered, and the solvent was removed. The residue was purified by chromatography on silica gel with petroleum ether/ethyl ester (v/v = 15:1) to give 2,6-dibromo-4-chlorobenzenamine (0.94 g, 66% yield). 1H NMR (400 MHz, CDCl3): δ 4.55 (s, 2H, -NH2), 7.38 (s, 2H, C6H2Br2ClNH2). 13C NMR (400 MHz, CDCl3): δ 108.43 (benzenamine carbon connected with Br), 130.48 (benzenamine carbon connected with Cl), 131.46 (benzenamine carbon), 141.25 (benzenamine carbon connected with NH2). | |
With triethylamine In dichloromethane at 0 - 25℃; for 1h; | ||
97 %Chromat. | With silver nanoparticle embedded mesoporous polyaniline nanocomposite at 140℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In acetonitrile at 20℃; for 0.166667h; | |
94% | In acetonitrile at 20℃; for 0.166667h; | |
94% | With hydroxyapatite supported copper(I) oxide In acetonitrile at 50℃; for 0.133333h; | General procedure for N-acetylation of amines usingHAP-Cu2O General procedure: To a mixture of amine (1 mmol), acetyl chloride (1 mmol)in acetonitrile (5 mL) were added hydroxyapatite -Cu2O(0.1 g) under air atmosphere. The reaction mixture wasrefluxed at 50 °C for an appropriate time. The progress ofthe reaction was monitored through TLC. Upon completionof the reaction, the reaction mixture was cooled toroom temperature and filtered. The residue was washedwith water followed by EtOAc (3 × 10 mL). The productwas obtained after the removal of solvent under reducedpressure followed by crystallization from pet ether orEtOAc:pet ether or passing through column of silica andelution with EtOAc:pet ether. |
91.9% | With potassium carbonate In propan-2-one at 0 - 30℃; for 11h; | |
91% | With mesoporous silica at 20℃; for 1.5h; Green chemistry; chemoselective reaction; | |
90% | With pyridine for 0.916667h; Cooling with ice; | |
81% | With triethylamine In dichloromethane at 0 - 25℃; | |
80% | With thermally decomposed Ni-Fe-hydrotalcite at 26.84℃; for 0.0833333h; Neat (no solvent); | |
With N-ethyl-N,N-diisopropylamine In dichloromethane | ||
In dichloromethane; water monomer | ||
With triethylamine In dichloromethane at 0 - 20℃; | ||
With triethylamine In dichloromethane at 0℃; Inert atmosphere; | ||
With triethylamine In dichloromethane at 0 - 20℃; | ||
In water monomer; acetonitrile for 0.166667h; | General Procedure of Preparation of Amide Compounds General procedure: All acyl chloride solutions were freshly prepared in acetonitrile (ACN) at 1 mg/mL. All amine solutions were freshly prepared in water (H2O) at 1mg/mL. A portion of each acyl chloride solution was mixed with an amine solution with an equal volume and the mixture was allowed to stand for about 10 min. Each mixture was diluted with ACN 10-fold for analysis. | |
With triethylamine In dichloromethane at 0 - 20℃; | General Procedure for the synthesis of Anilide Substrates from Anilines General procedure: To a solution of aniline (10 mmol) in anhydrous CH2Cl2 (20 mL) was added triethylamine (12 mmol) and benzenesulfonyl chloride / trifluoromathanesulfonyl chloride / benzoyl chloride / acetyl chloride (11 mmol) at 0 °C. The reaction mixture was stirred at room temperature until the reaction was completed (monitored by TLC). Water (50 mL) was added to the mixture and extracted with CH2Cl2 (30 mL). The organic phase was dried over anhydrous MgSO4, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel or recrystalization to afford the corresponding products in 85~96% yield. | |
With triethylamine In dichloromethane at 20℃; | ||
With 4-dimethylaminopyridine; triethylamine In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere; | ||
With triethylamine In dichloromethane at 0 - 20℃; for 10h; | ||
Stage #1: 4-chloro-aniline With triethylamine In dichloromethane for 0.166667h; Cooling with ice; Stage #2: acetyl chloride In dichloromethane for 2.25h; | ||
With triethylamine In dichloromethane at 0 - 20℃; Schlenk technique; | ||
With glacial acetic acid In dichloromethane; water monomer at 0 - 60℃; for 0.5h; | General procedure for reductive acetylation of nitroarenes General procedure: In a round-bottomed fask, a reaction mixture of nitrobenzene (1mmol), Cu or 4 wt% Cu-SiO2 (0.15 g) and NaBH4 solution (0.018 M) was stirred at room temperature. The complete conversion to aniline was confrmed by 1 H NMR. To the same solution maintained at 0°C, 3mL of dichloromethane was added followed by acetic acid (6.5mmol) and acetyl chloride (6.5mmol). The reaction was continued for 10min. Later the reaction mixture was kept in a water bath for a few minutes at 60°C. The process was repeated with a slight excess of acetic acid and acetyl chloride. The catalyst was separated using dichloromethane and the organics were washed with 0.1M NaOH. Organics were concentrated under reduced pressure and the residue was purifed through the column using hexane and ethyl acetate as an eluent. A similar procedure was followed for other derivatives. | |
With glacial acetic acid In dichloromethane; water monomer at 0 - 60℃; for 0.5h; | General procedure for reductive acetylation of nitroarenes General procedure: In a round-bottomed fask, a reaction mixture of nitrobenzene (1mmol), Cu or 4 wt% Cu-SiO2 (0.15 g) and NaBH4 solution (0.018 M) was stirred at room temperature. The complete conversion to aniline was confrmed by 1 H NMR. To the same solution maintained at 0°C, 3mL of dichloromethane was added followed by acetic acid (6.5mmol) and acetyl chloride (6.5mmol). The reaction was continued for 10min. Later the reaction mixture was kept in a water bath for a few minutes at 60°C. The process was repeated with a slight excess of acetic acid and acetyl chloride. The catalyst was separated using dichloromethane and the organics were washed with 0.1M NaOH. Organics were concentrated under reduced pressure and the residue was purifed through the column using hexane and ethyl acetate as an eluent. A similar procedure was followed for other derivatives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With ammonium molybdate; lithium hydroxide monohydrate; HNO3 In chloroform for 6h; Heating; | |
93% | With nickel(II) ammonium disulfate; HNO3 In chloroform; lithium hydroxide monohydrate at 20℃; for 3h; | |
93% | With tert.-butylnitrite at 25℃; for 4h; | 1; 7-8 Add 0.2 mmol p-chloroacetanilide, 0.6 mmol tert-butyl nitrite, 2 mL solvent hexafluoroisopropanol and a No. 5 reaction magnet in turn to the reactor and mix, pass the condensed water through the condenser tube from bottom to top, and place the reactor in the reactor. The reaction solution was stirred at 25° C. for 4 h to obtain a reaction solution containing 2-nitro-4-chloroacetanilide compound; further, the speed of the stirring reaction was 500 revolutions/min.This example also includes further purification of the 2-nitro-4-chloroacetanilide compound: pour the reaction solution containing the 2-nitro-4-chloroacetanilide compound into a separatory funnel, add 15 mL of distilled water, add 10 mL of ethyl acetate The ester was extracted three times, and the organic phase was distilled under reduced pressure to obtain the crude product, which was separated and purified by column chromatography to obtain the 2-nitro-4-chloroacetanilide compound in a yield of 93%. |
60% | With iron (ΙΙΙ) nitrate nonahydrate; NHPI In 1,2-dichloro-ethane at 50℃; for 10h; regioselective reaction; | |
55% | 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). |
With lithium hydroxide monohydrate; HNO3 | ||
With sulfuric acid; HNO3 | ||
With NaNO3; sulfuric acid | ||
With HNO3 | ||
With HNO3 at -10℃; | ||
With sulfuric acid; HNO3 1.) 0 deg C, 10 min, 2.) RT, 30 min; | ||
With HNO3; acetic anhydride In dichloromethane | ||
With HNO3; glacial acetic acid at 0℃; for 0.5h; | ||
With HNO3; acetic anhydride; glacial acetic acid at 0 - 25℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With Lawessons reagent In toluene at 90 - 110℃; for 2.5h; Inert atmosphere; | |
With tetraphosphorus decasulfide; potassium sulfide; xylene | ||
With phosphorous (V) sulfide; xylene |
With Lawessons reagent | ||
With Lawessons reagent In tetrahydrofuran at 50℃; for 2.5h; | 4.2.1. N-(p-Methylphenyl)benzenecarbothioamide (1f) General procedure: Preparation of thioamide 1f is described as a typical procedure. To a THF solution (50 mL) of Lawesson’s reagent (432 mg, 1.07 mmol) was added a solution of N-(p-methylphenyl)benzenecarboxamide (461 mg, 2.18 mmol) at room temperature. The reaction mixture was stirred and heated to 50 °C for 2.5 h. After cooling the resulting mixture to room temperature, the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate = 2:1) to give thioamide 1f (481 mg, 97% yield). | |
With Lawessons reagent In 1,4-dioxane at 110℃; | 4. General procedure for the synthesis of thioacetamides (12a-e) General procedure: The acetamides (11a-e, 10mmol) were refluxed with Lawesson’s reagent (7mmol) in dioxane for 3h. After completion of the reaction, dioxane was removed under reduced pressure, water was added and the product was extracted using ethyl acetate. The product was purified using column chromatography on silica gel 60-120 mesh to afford pure 12a-e in good yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With sodium nitrate; dipotassium peroxodisulfate In acetonitrile at 140℃; for 48h; 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 beim Nitrieren; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With N-Bromosuccinimide In acetonitrile for 2h; Irradiation; regioselective reaction; | |
95% | With hydrogen bromide; Selectfluor In water at 20℃; for 3.5h; regioselective reaction; | II. Bromination of anilides 1 General procedure: 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). |
79% | With N-Bromosuccinimide; cobalt acetylacetonate; trifluoroacetic acid; silver(l) oxide In 1,2-dichloro-ethane at 60℃; for 16h; regioselective reaction; |
75% | With N-Bromosuccinimide; methanesulfonic acid; nickel(II) chloride hexahydrate In water 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. |
69% | With N-Bromosuccinimide; 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 4h; Inert atmosphere; Sealed tube; | |
With perchloric acid; mercury(II) diacetate; N-bromoacetamide In water at 35℃; δE(excit.), ΔH(excit.), ΔS(excit.); further reaction partners: Cl(-), Br(-); | ||
With hydrogen bromide; nitric acid | ||
With bromine; sodium acetate; acetic acid at 70℃; | ||
With water; bromine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With 40% potassium fluoride/alumina at 85℃; for 0.0666667h; Microwave irradiation; Neat (no solvent); | |
99% | With ammonium bromide; ethylenediamine at 70℃; for 5h; Microwave irradiation; Inert atmosphere; neat (no solvent); | |
92% | Stage #1: N-(4-chlorophenyl)acetamide With Schwartz's reagent In tetrahydrofuran at 20℃; for 0.05h; Inert atmosphere; Stage #2: With water In tetrahydrofuran Inert atmosphere; |
87% | With pepsin immobilized on terephthalaldehyde functionalized chitosan magnetic nanoparticle In acetonitrile at 20℃; for 48h; | Deacetylation of Amides General procedure: To a solution of an amide (1 mmol) in 10 mL of acetonitrile and 10 mLof citrate buffer (pH = 2.0) was added the catalyst (100 mg). The reactionmixture was stirred at rt, and the progress of the reaction was monitored byTLC using ethyl acetate/n-hexane 50:50 as the eluent. After 48 h, the catalystswere removed and washed with HCl (0.01M). The crude residue was purifiedby preparative silica gel plate chromatography using ethyl acetate/n-hexane 50:50 as the eluent. The recovered catalyst was used for the next reaction cycleby the same procedure described above. |
With potassium carbonate | ||
With sodium hydroxide; cetyltrimethylammonim bromide In water at 71.5℃; var. reagents concentrations; | ||
With Rsp3690 from Rhodobacter sphaeroides In dimethyl sulfoxide at 30℃; Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With C20H25Cl2CoN3; sodium triethylborohydride; In 1,2-dimethoxyethane; at 100℃; for 6h;Inert atmosphere; | Under an inert atmosphere, the substrate 4-chloroacetanilide (170 mg, 1 mmol), polymethylhydrosiloxane (668 μL, 3 mmol), Co-2 catalyst (9.0 mg, 0.02 mmol), sodium triethylborohydride (40 μL, 0.04 mmol)were sequentially added to the reaction tube and ethylene glycol dimethyl ether (2 mL), and the resulting mixture was stirred well.The reaction was carried out in an oil bath at 100C for 6 hours. The reaction system was cooled to room temperature, diluted and quenched by adding ethyl acetate, and concentrated. The crude product was subjected to flash silica gel column chromatography to obtain 109 mg of light yellow oily liquid, yield: 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.9% | With N-chloro-N-(phenylsulfonyl)benzenesulfonamide In acetonitrile at 20 - 25℃; for 0.166667h; Green chemistry; | General procedure for the monochlorination reaction General procedure: To a solution of 4-nitroaniline, 1a (0.99 g, 7.2 mmol) in 7 mL specially dried MeCN was added N-chloro-N-(phenylsulfonyl)benzene sulfonamide (2.4 g, 7.2 mmol) in a 25 mL round bottom flask. The reaction mixture was stirred for 10-15 minutes at 20-25 °C (0 °C for 1-methyl-1H-imidazole, and N-methylindole), monitored by GC. After completion of the reaction, MeCN was distilled under vacuum at 40-45 °C. The residue was treated with 20 mL mixture of MDC and water, stirred the mixture for 10-15 minutes; MDC layer was separated and washed with 5 % sodium bicarbonate solution, after separation MDC layer was dried over sodium sulfate and evaporated under vacuum to obtain 2-chloro-4-nitroaniline, 2a, 1.22 g (98.5 % yield, 98.9 % purity) as a yellow powder. |
92% | With hydrogenchloride; N-chloro-2,2,6,6-tetramethylpiperidine In benzene at 50 - 60℃; | |
86% | With sodium perborate; potassium chloride In glacial acetic acid at 20℃; for 1.08333h; |
86% | With CAN; acetyl chloride In acetonitrile at 20℃; for 8h; | |
85% | With Chlorodimethylsulfonium chloride In dichloromethane at -25℃; for 4h; | |
81% | With hydrogenchloride; (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; hydrogen bromide; oxygen In lithium hydroxide monohydrate; acetonitrile at 25℃; for 1h; Irradiation; regioselective reaction; | |
79% | With calcium hypochlorite In lithium hydroxide monohydrate; glacial acetic acid; propan-2-one at 0℃; for 1h; | |
78% | With lead tetraacetate; anhydrous tin tetrachloride In ethyl acetate for 20h; | |
75% | With hydrogen fluoride; antimony pentafluoride; sodium chloride at -20℃; for 2h; | |
74% | With trichloroisocyanuric acid; brilliant green In acetonitrile at 20℃; for 2h; Irradiation; regioselective reaction; | |
71% | With [bis(acetoxy)iodo]benzene; sodium chloride for 0.5h; | |
62% | With potassium peroxomonosulfate; potassium chloride In lithium hydroxide monohydrate; acetonitrile at 20℃; | |
53% | With (Dichloroiodo)benzene; (2,2,2-trifluoroacetyl)oxysilver In ethanol at 25℃; for 0.166667h; Green chemistry; regioselective reaction; | |
With hydrogenchloride; lithium hydroxide monohydrate; glacial acetic acid; calcium(II) chloride | ||
With chlorine; 1,1,2,2-tetrachloroethane | ||
With hydrogenchloride; dihydrogen peroxide Chlorieren; | ||
With lithium hydroxide monohydrate; chlorine | ||
With chlorine; benzene | ||
With glacial acetic acid; calcium(II) chloride | ||
With potassium hypochlorite; glacial acetic acid | ||
With N-chloro-succinimide; lithium chloride In glacial acetic acid | ||
280 kg | Stage #1: acetanilide With sulfonic chloride acid; sulfur trioxide at 25 - 30℃; for 2h; Large scale; Green chemistry; Stage #2: With thionyl chloride at 445℃; for 4h; Large scale; Green chemistry; | 1 In the sulfonation reaction pot by adding 2500kg chlorosulfonic acid, the temperature dropped to below 30 degrees,Adding 300 kg of sulfur trioxide, stirring reaction for 2 hours, the temperature to 25 degrees below,Began to cast acetanilide 1100kg, feeding process to maintain the temperature below 30 degrees, feeding the end,Insulation reaction 2 hours, the end of the reaction, through the dry air will be the system of excess sulfur dioxide blowing,Into the hydrogen chloride-containing reactor, the chlorosulfonic acid synthesis,To obtain 280 kg of chlorosulfonic acid recovered (for the next sulfonation reaction).And then remove the sulfur trioxide from the material to about 45 degrees, dropping 1000kg of thionyl chloride,Dropping process to keep the temperature at about 45 degrees, after the end of feeding, the insulation reaction 4 hours,The content of chloroacetanilide was measured and the result was 250 ppm / kg.And then further added 850kg sodium sulfite for reduction,Followed by the addition of 700 kg of ethylene oxide for condensation,The resulting product was condensed with 700 kg of sulfuric acid to give 2050 kg of the finished product,Purity of 97.5%, p-(β-sulfatoethylsulfonyl)aniline for 125ppm / kg,Suitable for bitter quality requirements. |
8 %Chromat. | With N-chloro-succinimide; urea In acetonitrile at 20℃; for 2h; | 5 5.2. General procedure for bromination General procedure: Reaction conditions: Thiourea (5.1 mol%, 2 mg, 0.026 mmol) was added to an acetonitrile solution (10 mL) containing NBS (1.15 equiv, 104.4 mg, 0.587 mmol). Anisole (56.3 mg, 0.51 mmol) was added immediately to the resulting stirred solution and allowed to stir at room temperature for 10 min. The reaction was quenched by the addition of 10% aqueous solution of Na2S2O3 (10 mL) and extracted with ethyl acetate (70 mL). The organic solution was then washed with additional 10% Na2S2O3 (2 * 10 mL), followed by deionized water (3 * 15 mL) and brine (2 * 10 mL). The organic solution was then dried over anhydrous Na2SO4 and the solvent was evaporated in vacuo. The major product of each reaction was isolated by centrifugal thin-layer chromatography using a 2 mm thick silica gel 60GF254 coated plate (5% CH2Cl2/hexanes). The products reported herein are known compounds and were characterised by GC-MS, IR, 1H and 13C NMR. Their spectroscopic data are in agreement with those reported in the literature. |
36 %Spectr. | With N-chloro-succinimide In acetonitrile at 20℃; for 24h; regioselective reaction; | 4.2. General procedure for the chlorination of arenes and heteroarenes General procedure: To an oven-dried flask was added a magnetic stir bar, methylene green (9.1 mg, 0.05 equiv, 0.025 mmol), ammonium peroxodisulfate (11.4 mg, 0.1 equiv, 0.05 mmol), arene/heteroarene (1 equiv, 0.5 mmol), acetonitrile (2.5 mL), and then N-chlorosuccinimide (73.4 mg, 1.1 equiv, 0.55 mmol). The reaction mixture was stirred open to air at room temperature (20 C) in a white LED chamber for 24 h. For substrates that produced a mixture of mono- and dibrominated products upon full conversion, 2.2 equivalents (1.1 mmol) of N-chlorosuccinimide was employed. Upon completion of the reaction, the crude mixture was evaporated under pressure and the chlorinated product was isolated via column chromatography on silica gel. |
65 %Spectr. | With dichloromethane; CsPbCl3; N-ethyl-N,N-diisopropylamine Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With p-toluenesulfonyl chloride In acetonitrile for 2h; Inert atmosphere; Reflux; | |
97% | With 1,3,5-trichloro-2,4,6-triazine at 60℃; for 2.7h; Ionic liquid; regioselective reaction; | 4.3. Typical procedure for the TCT-catalyzed Beckmann rearrangement General procedure: In a dry flask, ketoxime 1a (118 mg, 0.6 mmol) was dissolved in the ionic liquid 3b (2 mL, 2.34 g) and 2,4,6-trichlorotriazine was added (6.2 mg, 0.034 mmol). After stirring for 40 min at 60 °C the reaction mixture was directly extracted with MTBE by a liquid-liquid continuous extraction apparatus. The resulting MTBE solution of 2a was filtered over a silica plug (eluant AcOEt/PE 1:4) to remove trace amounts of 3b. Evaporation of the solvent under reduced pressure afforded 106 mg of N-phenyl-benzamide (2a) (106 mg, 90%), as a white solid, mp 164 °C (lit.20 164-165 °C). After removal of trace amounts of MTBE, followed by drying under vacuum, the IL residue 3b (2.20 g, yield 95%) could be reused for further reactions.Alternatively, the crude reaction mixture was directly subjected to column chromatography on silica gel (eluant AcOEt/PE 1-7) to give of N-phenyl-benzamide (2a) (111 mg, 94%). The ionic liquid 3c was quantitatively recovered by eluting with AcOEt/MeOH (1:1).The same procedure was used to generate amides 2b-g, as pure compounds, whose physical and spectroscopic data match those previously reported.21 |
97% | With [bis(acetoxy)iodo]benzene; boron trifluoride diethyl etherate In acetonitrile at 70℃; for 4h; | The experimental Procedures and Characterization Data General procedure: The solution of PhI(OAc)2 (0.48 mmol) and BF3·Et2O (0.96 mmol)in CH3CN (1.0 mL) was stirred at 70 °C for 30 min. Then pmethoxyacetophenone(1a, 0.40 mmol) was added to the abovemixture and stirred 70 °C for 5 min. Cooling to r.t., 0.5% aqNa2SO3 was added to the reaction mixture and extracted withCHCl3. Combined organic layer was washed with water, driedover Na2SO4, and concentrated in vacuo. The residue was purifiedby SiO2 column chromatography (n-hexane/AcOEt = 1:1)and preparative TLC (n-hexane/AcOEt = 5:1) to give N-(4-methoxyphenyl)acetamide (2a, 97%) as white solid.N-(4-Methoxyphenyl)acetamide (2a)White solid. |
96% | With phosphotungstic acid In acetonitrile for 2.08333h; 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. |
95% | Stage #1: 4-chloroacetophenone oxime With fluorosulfonyl fluoride; triethylamine In acetonitrile at 20℃; Stage #2: With hydrogenchloride In water; acetonitrile at 20℃; | |
95% | With ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate In acetonitrile at 85℃; Microwave irradiation; Inert atmosphere; | |
94% | With neodymium(III) trifluoromethanesufonate In acetonitrile for 1.5h; Heating; | |
94% | With trifluoromethylsulfonic anhydride In dichloromethane at 20℃; for 3.5h; Inert atmosphere; | |
92% | With trimethylsilylphosphate In dichloromethane for 3.5h; Ambient temperature; | |
92% | With aminosulfonic acid; zinc(II) chloride In acetonitrile at 90℃; for 2h; | |
92% | With C82H80N4O6; mercury dichloride In tetrahydrofuran; water; acetonitrile at 20℃; for 1h; | |
92% | With sulfonated polymeric solid acid H-PDVB-SO3H In benzonitrile at 130℃; for 1h; | |
91% | With yttrium(III) trifluoromethanesulfonate In acetonitrile for 1.5h; Heating; | |
90% | With 1,3,5-trichloro-2,4,6-triazine at 60℃; for 5h; | |
90% | With tin(II) chloride dihdyrate; tetra-(n-butyl)ammonium iodide In acetonitrile for 0.5h; Molecular sieve; Reflux; | |
90% | With 2-chloro-1-methyl-pyridinium iodide; triethylamine In acetonitrile at 20℃; for 0.0833333h; | 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 carbon tetrabromide; N,N-dimethyl-formamide In acetonitrile for 12h; Inert atmosphere; Irradiation; Sealed tube; | |
87% | 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. |
86% | With aluminium trichloride; silica gel; zinc(II) chloride In dichloromethane for 0.133333h; microwave irradiation; | |
84% | With ruthenium trichloride In acetonitrile for 3h; Heating; | |
80% | With dihydrogen phosphate for 0.025h; microwave irradiation; | |
75% | With O-phenyl phosphorodichloridate In acetonitrile at 20℃; for 13h; | |
75% | With carbon tetrabromide; triphenylphosphine In toluene at 80℃; for 1h; Inert atmosphere; | |
74% | With ammonium peroxydisulfate; dimethyl sulfoxide In 1,4-dioxane at 100℃; for 8h; Schlenk technique; Inert atmosphere; | |
73% | With indium(III) triflate for 0.0166667h; Microwave irradiation; Ionic liquid; | |
68% | With 1,3,5-trichloro-2,4,6-triazine In dimethyl sulfoxide; acetonitrile at 0℃; for 6.5h; | 1.3 Synthesis of amides by rearrangement of ketoximes General procedure: In a general procedure, 20 mL of glass vial was charged with 156 mg of DMSO (2 mmol) and 368 mg of TCT (2 mmol). The reagents were dissolved in 6 mL of MeCN (AR, >99%) and stirred at ice-base for 10 min. Ketoxime (2 mmol) in 2 mL of MeCN was added in. The reaction was monitored by TLC until the one substrate consumed. Volatiles were removed under vacuum. The residues were re-dissolved in ethyl acetate and extracted firstly by saturated aqueous sodium carbonate, then dilute hydrochloride (1 N) and finally saturated aqueous sodium chloride. The pure product was obtained by silica-filled flash column chromatography. |
64% | With iron(III) chloride; silver hexafluoroantimonate In 1,2-dichloro-ethane at 80℃; for 24h; | Iron-Catalyzed Beckmann Rearragnment; General Procedure General procedure: To an oven-dried 20 mL vial containing FeCl3 (24.3 mg,0.15 equiv), was added a solution of oxime (1 mmol) in DCE (10mL) and the mixture was stirred until FeCl3 was completely dissolved(10-15 min). To this solution was added AgSbF6 (154.6mg, 0.45 equiv), then the vial was capped and put into mechanicalshaker at 80 °C for 24 h. The mixture was filtered throughCelite with CH2Cl2 (100 mL) and concentrated to give a residue,which was purified by silica flash chromatography usinghexanes and ethyl acetate in appropriate combination based onthe Rf of the desired product. |
63% | With montmorillonite KSF; montmorilonite In toluene for 10h; Heating; | |
60% | With aluminum (III) chloride In acetonitrile for 2h; Inert atmosphere; Reflux; | |
60% | With boron trifluoride diethyl etherate In acetonitrile for 3h; Inert atmosphere; Reflux; | |
45% | With tris(2,2'-bipyridyl)ruthenium dichloride; carbon tetrabromide; N,N-dimethyl-formamide at 50℃; for 0.833333h; Flow reactor; | |
35% | With 10-methyl-9-phenylacridin-10-ium perchlorate In 1,2-dichloro-ethane at 20℃; for 5h; Irradiation; Sealed tube; | |
33% | With chlorotropylium chloride In acetonitrile at 80℃; for 3h; Inert atmosphere; | |
With boron trifluoride diethyl etherate; 1-n-butyl-3-methylimidazolim bromide at 120℃; for 3h; Inert atmosphere; | ||
With perchloric acid supported over silica In dichloromethane at 20℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With hydrogen at 100℃; for 24h; Sealed tube; | |
85% | 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. |
80% | With Methyl formate at 180℃; for 8h; |
47% | With carbon monoxide; tin(IV) chloride In 1,4-dioxane at 180℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7.5%; 84.5% | With 1,3-bis(1-adamantyl)imidazolium tetrafluoroborate; N-chloro-succinimide; camphor-10-sulfonic acid; In 1,4-dioxane; at 25℃; for 24h; | General procedure: A mixture of Acetylaniline (0.2 mmol), NCS (0.26 mmol), D-CSA (0.1 mmol) and 1,3-di(1-adamantl)imidazolium tetrafluoroborate (0.01 mmol) in dioxane (1 mL) wasstirred at room temperature (25 oC) under air atmosphere for 24h. The reactionmonitored by GC-MS. When the acetylaniline was consumed completely, the reactionmixture was quenched with saturated aq. NaHCO3 (4 mL). The resulting mixture wasextracted with EtOAc (4 mL x 3). The organic layer was washed with pure water (4ml x 3). The combined organic layer was dried over anhydrous Na2SO4, filtered andthe solvent was removed under reduced pressure to provide the crude product. Thepurification was performed by flash column chromatography on silica gel. |
24%; 75% | With N-chloro-succinimide; chloro-trimethyl-silane; In acetonitrile; at 20℃; for 1h; | General procedure: To a solution of 4-bromoanisole (200.8 mg, 1.09 mmol, 1.0 equiv) in acetonitrile (2 mL) was added N-chlorosuccinimide(NCS) (158.3 mg, 1.19 mmol, 1.1 equiv) at rt to give a slightly cloudy mixture. Chlorotrimethylsilane (TMSCl) (14 muL, 0.11 mmol, 0.1 equiv) was then added drop-wise to the reaction mixture. Within a few minutes, the reaction mixture became clear pale yellow solution. The mixture continued to stir at rt for 1 h and was diluted with hexane. The biphasic mixture was concentrated on a rotary evaporator to a crude white solid-oil mixture. This mixture was taken up in hexane and filtered through a short plug of SiO2 and eluted with 5-10% EtOAc-hexane solution. The clear filtrate was concentrated to obtain a mixture of 4-bromo-2-chloro-1-methoxybenzene (2a-Cl) and 2,4-dichloro-1-methoxybenzene (2a-diCl) 237.0 mg (88% of 2a-Cl and 11% of 2a-diCl,based on NMR ratio 2a-Cl: 2a-diCl = 7.1: 1.0; as a pale yellow solid). |
20%; 69% | With ammonium persulfate; N-chloro-succinimide; oxygen; methylene green; In acetonitrile; at 20℃; for 24h;Irradiation; | General procedure: To an oven-dried flask was added a magnetic stir bar, methylene green (9.1 mg, 0.05 equiv, 0.025 mmol), ammonium peroxodisulfate (11.4 mg, 0.1 equiv, 0.05 mmol), arene/heteroarene (1 equiv, 0.5 mmol), acetonitrile (2.5 mL), and then N-chlorosuccinimide (73.4 mg, 1.1 equiv, 0.55 mmol). The reaction mixture was stirred open to air at room temperature (20 C) in a white LED chamber for 24 h. For substrates that produced a mixture of mono- and dibrominated products upon full conversion, 2.2 equivalents (1.1 mmol) of N-chlorosuccinimide was employed. Upon completion of the reaction, the crude mixture was evaporated under pressure and the chlorinated product was isolated via column chromatography on silica gel. |
With 4-chloromorpholine; ammonium peroxydisulfate; tris(bipyridine)ruthenium(II) dichloride hexahydrate; In water; acetonitrile; at 25℃; for 16h;Irradiation; Inert atmosphere; | General procedure: In a 5mL crimp cap vial 0.25mmol of the respective substrate, together with 0.3mmol (1.2equiv) of the N-chloramine or NCS, 0.3mmol (1.2equiv) (NH4)2S2O8, and 2mol% (0.005mmol) [Ru(bpy)3]Cl2×6H2O were dissolved in 2mL of MeCN/water 4:1. The reaction mixture was degassed by three cycles of freeze-pump-thaw and irradiated for 16h with blue LEDs (lambdamax=455nm). For GC analysis 500muL of the reaction mixture was added to 500muL of the standard solution (0.1M), anisole for dimethoxybenzene, toluene for anisole, mixed, filtered and submitted to GC analysis. For Tables 4 and 5: After the irradiation the internal standard (0.01mmol n-pentadecane) was added to the reaction and the reaction was immediately quenched with satd Na2CO3-solution and brine. The mixture was extracted with ethyl acetate and subjected to GC-FID analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sodium dodecyl-sulfate; trichlorophosphate In acetonitrile for 1.5h; Heating; | |
65% | With trichlorophosphate In 1,2-dichloro-ethane at 40℃; for 1h; ultrasound irradiation; | |
45% | With trichlorophosphate at 85℃; for 24h; |
36% | With trichlorophosphate at 80 - 90℃; for 16h; | |
36% | Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 5℃; for 1h; Stage #2: N-(4-chlorophenyl)acetamide 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. |
With trichlorophosphate 1.) 0 deg C, 0.5 h, 2.) 70 deg C, 16 h; Multistep reaction; | ||
With trichlorophosphate at 5 - 75℃; for 4h; | 25 2,6-Dichloroquinoline-3-carbaldehyde POCl3 (31.1 g, 210 mmol) was added to DMF (6.5 g, 90 mmol) while keeping the temperature below 5° C. 4-Chloroacetanilide (5.07 g, 30 mmol) was added in one portion and the reaction mixture was heated to 75° C. for 4 hours. The reaction mixture was cooled to room temperature and poured onto ice. The separated crystals were filtered and dried. Yield 220 mg. M.p. 188-190° C. | |
With trichlorophosphate | ||
With trichlorophosphate at 0 - 75℃; for 6h; | ||
With trichlorophosphate | ||
With trichlorophosphate | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate Stage #2: N-(4-chlorophenyl)acetamide | ||
With trichlorophosphate Heating; | ||
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 80 - 100℃; | Step II Preparation of 2-chloro-3-formylquinoline CFQ 8, 9 General procedure: To a s o l u t i o n o f a c e t a n i l i d e(N-phenylacetamide) (5 mmoles) in dry DMF (15mmoles) at 0-5oC POCl3 (60 mmoles) was addeddropwise with stirring and the mixture was thenstirred at 80 - 100oC for time ranging between 4-16hr. The mixture was poured on to crush ice, stirredfor 5 minutes and the resulting solid fltered, washedwell with water and dried. The compounds wererecrystallized from ethyl acetate. Phosphoryl chloride(commonly called phosphorus oxychloride) is acolorless liquid with the formula POCl3. It hydrolysesin moist air to phosphoric acid to release choking fumes of hydrogen chloride. It is manufacturedindustrially on a large scale from phosphorustrichloride and oxygen or phosphorus pentoxide. Itis mainly used to make phospha (Table 1). | |
With trichlorophosphate | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: N-(4-chlorophenyl)acetamide at 80℃; for 18h; | ||
With trichlorophosphate at 0 - 82℃; for 24h; Inert atmosphere; | ||
With trichlorophosphate for 24h; Heating; | ||
With trichlorophosphate at 80 - 90℃; | ||
With trichlorophosphate at 0℃; for 16h; Reflux; | 2.3.1 General procedure for the synthesis of 6/7/8-substituted-2-chloro quinoline-3-carbaldehydes (2) General procedure: Dimethyl formamide (9.13g, 9.9ml, and 0.125mole)wasfrozento 0°C in a flask along with a drying tube and phosphoryl chloride (53.7g, 32.2ml. 0.35mole) was mixed drop wise with stirring. The substituted acetanilide (1) (6.55g, 0.05mole) was added to the mixture and the mixture was heated under reflux for 16h. The product obtained was added into ice cold water and stirred for 30min at 0-10°C. 6/7/8-Substituted-2-chloro quinoline-3-carbaldehyde (2) separated as yellow precipitate. It was filtered, washed with water and recrystallized from ethyl acetate. | |
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. | |
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.25h; Stage #2: N-(4-chlorophenyl)acetamide at 80℃; for 8h; | ||
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. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With XY-zeolite; hydroxylamine hydrochloride for 0.0416667h; microwave irradiation; | |
92% | With sodium azide; sulfuric acid; silica gel at 60℃; for 0.583333h; | |
92% | With O-benzenesulfonyl-acetohydroxamic acid ethyl ester; toluene-4-sulfonic acid In water; acetonitrile at 23℃; for 24h; Inert atmosphere; |
91% | With sodium hydrogen sulfate; hydroxylamine hydrochloride; silica gel for 0.0416667h; Heating; | |
90% | With phosphorus pentaoxide; sodium azide; silica gel for 0.133333h; microwave irradiation; | |
90% | With mesitylenesulfonylhydroxylamine In acetonitrile at 20℃; for 8h; | 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. |
90% | With hydroxylamine hydrochloride; water; Thiamine hydrochloride In 1,4-dioxane at 90℃; for 0.5h; | 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. |
89% | With hydroxylamine hydrochloride at 160℃; for 0.05h; microwave irradiation; | |
89% | 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. |
86% | With zinc(II) chloride; hydroxylamine-O-sulfonic acid In water at 80℃; for 8h; | 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. |
83% | With methanesulfonic acid; tetrabutylammoniun azide In 1,2-dimethoxyethane at 80℃; for 0.0833333h; Flow reactor; | |
62% | 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). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With palladium diacetate; potassium carbonate; XPhos In <i>tert</i>-butyl alcohol at 90℃; for 14h; | |
118 mg (98%) | In hexane | N-(4-p-Tolylaminophenyl)acetamide N-(4-p-Tolylaminophenyl)acetamide Following the general procedure, 4-chloroacetanilide (85 mg, 0.5 mmol) was coupled with p-toluidine (80 mg, 0.75 mmol) with the reaction temperature of 90° C. and the reaction time of 14 h. Chromatography on silica gel column with 2:1 hexane:ethyl acetate gave 118 mg (98%) of the title compound as a pink solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With lithium hexamethyldisilazane; 2,8,9-tris(2-methylpropyl)-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane In tetrahydrofuran; toluene at 100℃; for 32h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With lithium hexamethyldisilazane; 2,8,9-tris(2-methylpropyl)-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane In tetrahydrofuran; toluene at 100℃; for 28h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With palladium diacetate; Selectfluor; trifluoroacetic acid In 1,2-dichloro-ethane at 20℃; for 4h; | 4 4.3. General procedure B: procedure for the alkenylation reaction General procedure: A solution of anilides, alkene, Selectfluor, Pd(OAc)2, TFA or methanesulfonic acid in DCE was stirred at room temperature. After the reaction was completed, the mixture was extracted with EtOAc (10 mL * 3). The organics were dried over Na2SO4. Then the solvent was removed under reduced pressure to provide the crude product. The purification was performed by flash column chromatography on silica gel. |
32% | With tert-Butyl peroxybenzoate; copper diacetate; palladium diacetate; toluene-4-sulfonic acid; acetic acid at 20℃; for 16.05h; | |
25% | With 1,4-benzoquinoline; toluene-4-sulfonic acid In acetic acid; toluene at 22℃; for 17h; |
11 % Spectr. | With copper diacetate; oxygen; toluene-4-sulfonic acid In acetic acid; toluene at 60℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium carbonate at 150℃; for 4h; | |
91% | With potassium carbonate at 150℃; for 4h; | In one example, under nitrogen gas, a stirred mixture of 4-Chloro-l -nitrobenzene (e.g., about lg, 6.35 mmol), thioacetic acid (e.g., about 1.93g, 25.39 mmol), K2CO3 (e.g., about 0.050 g, 0.36 mmol), and dry Triton - X 405 (e.g., about O.O1Og) were heated at about 150 DEG C. The progress of the reaction was monitored by HPLC and GC. After four hours the reaction was cooled to room temperature, and acetone (e.g., about 8 mL) was added and filtered through a sintered glass funnel. Evaporation of the acetone produced about 0.975g of N-(4-Chloro-phenyl)-acetamide (e.g., about 91%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With silver fluoride; copper(II) bis(trifluoromethanesulfonate) In 1,4-dioxane at 110℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With pyridine; diphenyl phosphoryl azide for 16h; Reflux; Inert atmosphere; | |
96% | With diphenyl phosphoryl azide In pyridine for 16h; Reflux; Inert atmosphere; | Synthesis of 1,5-disubstituted tetrazoles General procedure: DPPA or p-NO2DPPA (0.4mmol) was added to a solution containing the amide (0.2mmol) in pyridine or 4-methylpyridine (0.3mL) under an N2 atmosphere. After stirring for 16h at reflux (oil bath), the mixture was diluted with AcOEt (30mL). The mixture was washed with 1N HCl, water, saturated aqueous NaHCO3, and brine (25mL), and then dried over Na2SO4. Concentrating the solvent in vacuo followed by purification of the residue on a silica gel column (AcOEt:n-Hexane 1:1-1:4) gave the desired tetrazole. |
Multi-step reaction with 2 steps 1: PCl5 2: HN3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium phosphate In <i>tert</i>-butyl alcohol at 110℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: p-chlorobenzenediazonium tetrafluoroborate; acetonitrile for 0.0166667h; Microwave irradiation; Stage #2: With water In diethyl ether | |
68% | With potassium phosphate; copper(l) iodide In water at 80℃; for 12h; Schlenk technique; | 16 Preparation of 4-chloroacetanilide: A 113.5 mg (0.5 mmol) of 4-chlorophenyl diazonium tetrafluoroborate, 0.1mmol cuprous iodide, and 0.5 mmol of potassium phosphate and 1.0 mmol of water in a nitrogen atmosphere Schlenk tube was added, 1 mL of acetonitrile under air conditions at 80 °C was stirred for 12 hours, the reaction yield of 68%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; silver trifluoromethanesulfonate; silver carbonate In 1,2-dichloro-ethane at 90℃; for 12h; chemoselective reaction; | |
73% | With dipotassium peroxodisulfate; palladium diacetate; trifluoroacetic acid In dichloromethane at 20℃; for 20h; | |
73% | With tert.-butylhydroperoxide; palladium(II) trifluoroacetate; silver trifluoromethanesulfonate In toluene at 120℃; for 24h; | 2.1. Typical procedure for the synthesis of anilides with olefins: General procedure: The mixture of 4-methyl-N-phenylbenzamide (1a) (0.5 mmol), ethyl Acrylate (2a) (0.7 mmol), Pd (TFA)2 (5 mol%), AgOTf (25 mol%) and TBHP (1.5 equiv.) in toluene (3 mL) was stirred at 120 °C under air for 24 h. Upon completion, the reaction mixture was removed the solvents to give the residue. The residue was then purified by column chromatography on silica gel (ethyl acetate / petroleum ether = 1:10) to provide the corresponding product as white solid 3a. |
70% | With dipotassium peroxodisulfate; palladium diacetate; trifluoroacetic acid In dichloromethane at 25℃; for 36h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In dimethyl sulfoxide at 100℃; for 16h; diastereoselective reaction; | General procedure: To a stirred solution of indole (1.0 mmol)/Imidazole (1.2 mmol) in DMSO was added 1,3-diyne (1.0 mmol), CuI (0.1 mmol), 1,10-phenanthroline (0.05 mmol) and cesium carbonate (1.5 mmol). The reaction mixture was heated at 100 °C for 5-16 h and the completion of the reaction was monitored by TLC. After completion of the reaction, it was cooled down to room temperature and then diluted with H2O (5 mL) followed by extraction of the product with EtOAc (3 × 10 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and the solvent was removed in vacuo. The crude product was purified on a silica gel column using hexane: ethyl acetate as eluent. The Z isomer was crytalised using DCM/EtOH in indole and EtOH in case of imidazole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In dimethyl sulfoxide at 100℃; for 16h; diastereoselective reaction; | General procedure: To a stirred solution of indole (1.0 mmol)/Imidazole (1.2 mmol) in DMSO was added 1,3-diyne (1.0 mmol), CuI (0.1 mmol), 1,10-phenanthroline (0.05 mmol) and cesium carbonate (1.5 mmol). The reaction mixture was heated at 100 °C for 5-16 h and the completion of the reaction was monitored by TLC. After completion of the reaction, it was cooled down to room temperature and then diluted with H2O (5 mL) followed by extraction of the product with EtOAc (3 × 10 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and the solvent was removed in vacuo. The crude product was purified on a silica gel column using hexane: ethyl acetate as eluent. The Z isomer was crytalised using DCM/EtOH in indole and EtOH in case of imidazole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In dimethyl sulfoxide at 100℃; for 16h; diastereoselective reaction; | General procedure: To a stirred solution of indole (1.0 mmol)/Imidazole (1.2 mmol) in DMSO was added 1,3-diyne (1.0 mmol), CuI (0.1 mmol), 1,10-phenanthroline (0.05 mmol) and cesium carbonate (1.5 mmol). The reaction mixture was heated at 100 °C for 5-16 h and the completion of the reaction was monitored by TLC. After completion of the reaction, it was cooled down to room temperature and then diluted with H2O (5 mL) followed by extraction of the product with EtOAc (3 × 10 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and the solvent was removed in vacuo. The crude product was purified on a silica gel column using hexane: ethyl acetate as eluent. The Z isomer was crytalised using DCM/EtOH in indole and EtOH in case of imidazole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 88% 2: 4% 3: 7% | With hydrogenchloride; sodium chlorate In water; acetic acid at 20℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With Br(1-)*C21H26N3S(1+); sodium carbonate In toluene at 80℃; for 0.3h; | 4.3.1. Typical procedure for synthesizing difluoromethyl imidates General procedure: To a toluene solution (1.5 mL) of 4·HBr (3.4 mg, 0.0098 mmol), sodium carbonate (4.2 mg, 0.040 mmol), and N-phenylcyclohexanecarboxamide 7d (39 mg, 0.19 mmol) was added TFDA (75 μL, 0.38 mmol) at room temperature. The reaction mixture was stirred and heated at 80 °C for 20 min. After cooling the resulting mixture to room temperature, aquaus NaOH was added to quench the reaction. Extraction with dichloromethane and purification by column chromatography (SiO2, hexane:AcOEt = 50:1, 0 °C) gave 8d (39 mg, 81% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tert.-butylhydroperoxide; palladium diacetate In dimethyl sulfoxide at 100℃; for 20h; regioselective reaction; | |
15% | 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. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 10 wt. % sulfated polyborate In neat (no solvent) at 120℃; for 4h; Green chemistry; | Representative procedure for transamidation of carboxamides General procedure: A mixture of amine (2.0 mmol), carboxamide (2.4 mmol) and sulfated polyborate (10 wt.%) was heated at 120° C. The reaction was monitored by thin-layer chromatography. After completion of the reaction, the mixture was cooled to room temperature and quenched with water; the precipitated solid was filtered at the vacuum pump, washed with water (3 x 5 mL), dried under vacuum and recrystallized from ethanol to afford the pure organic product. For liquid products (1g, 2e, and 3e), the reaction mixture was diluted with water and extracted with ethyl acetate (3 X 5 mL). The combined organic layers were washed with water, dried over sodium sulfate, filtered and evaporated under reduced pressure to get the crude products, which were purified by column chromatography using silica as the stationary phase and ethyl acetate/petroleum ether as the mobile phase. To recycle the catalyst, the aqueous quench and washes were saved and evaporated, then dried under vacuum. The solid thus obtained was treated as previously described43 and used in subsequent runs without significant loss of yield. |
86% | With [bis(acetoxy)iodo]benzene In neat (no solvent) at 120℃; for 0.333333h; Microwave irradiation; Green chemistry; | |
86% | With sulfated tungstate In toluene for 12h; Reflux; Green chemistry; |
86% | 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 |
83% | 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; | |
81% | With 1-(3-sulfopropyl)pyridinium phosphotungstate In neat (no solvent) at 120℃; for 1h; Microwave irradiation; | 4.3.4. N-(4-Chlorophenyl)acetamide (3d) 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. |
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 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Stage #1: N-(4-chlorophenyl)acetamide With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -20 - 20℃; for 0.416667h; Inert atmosphere; Stage #2: non-2-ynal In tetrahydrofuran at -78 - 20℃; for 0.5h; Inert atmosphere; | |
77% | Stage #1: N-(4-chlorophenyl)acetamide With n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; hexane at -20 - 20℃; Inert atmosphere; Stage #2: non-2-ynal In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; | Typical procedure for the aldol reaction General procedure: To a cooled solution of DIPA (2.1 equiv) in THF [0.2 M] at 20 Cand under argon was dropwise added n-BuLi (1.6 M in hexanes, 2.1 equiv). The resulting bright yellow solution was stirred at the same temperature for 5 min. The appropriate acetanilide derivative (1.0 equiv) was then added under argon flushing. The reaction mixture was warmed to room temperature and stirred for 20 min. The mixture was then cooled to 78 C and the appropriate aldehyde was dropwise added (viscous or solid aldehydes were dissolved in 5 mL THF). The reaction mixture was stirred at 78 C for 30 min, slowly warmed to room temperature, and stirred for 1 h. The reaction was then quenched with aqueous NH4Cl. Layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with 1 N HCl, water, brine, then dried over MgSO4, filtered, and concentrated in vacuo. The product was purified by recrystallization (Cyclohexane/EtOAcmixtures) or by flash chromatography (SiO2, Cyclohexane/EtOAc) to afford the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine In dichloromethane at 5℃; for 5h; Inert atmosphere; | 2 2.2 Synthesis of 2,6-dibromo-4-chlorobenzenamine 1b Acetic acid (2 ml) was added to a stirred solution of 4-chlorobenzenamine (0.64 g, 5 mmol) in CH2Cl2. The solution was stirred for 30 min. After the solution cooled to 5 °C with ice bath, Br2 (2.00 g, 12.5 mmol) in 5 ml CH2Cl2 was slowly added to the stirred solution. The mixture was stirred for 5 h and neutralized by 10% saturated aqueous sodium hydroxide solution. The mixture was extracted three times with 50 ml petroleum ether. The combined organic phase was dried over MgSO4, filtered, and the solvent was removed. The residue was purified by chromatography on silica gel with petroleum ether/ethyl ester (v/v = 15:1) to give 2,6-dibromo-4-chlorobenzenamine (0.94 g, 66% yield). 1H NMR (400 MHz, CDCl3): δ 4.55 (s, 2H, -NH2), 7.38 (s, 2H, C6H2Br2ClNH2). 13C NMR (400 MHz, CDCl3): δ 108.43 (benzenamine carbon connected with Br), 130.48 (benzenamine carbon connected with Cl), 131.46 (benzenamine carbon), 141.25 (benzenamine carbon connected with NH2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With dihydrogen peroxide In water at 25℃; for 8h; Green chemistry; | |
82% | With iodine; toluene-4-sulfonic acid In 1,4-dioxane at 140℃; for 24h; 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. |
77% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium t-butanolate In toluene at 100℃; for 16h; |
62% | With 2,2'-azobis(isobutyronitrile); oxygen In acetonitrile at 80℃; for 24h; Sealed tube; | 10 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. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | 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 |
---|---|---|
78% | With palladium diacetate; Selectfluor at 70℃; for 48h; | 3 4.4. General procedure C: procedure for the decarboxylative acylation reactions General procedure: A solution of anilides (0.2 mmol), α-oxocarboxylic acids (1 mmol), selectfluor (0.6 mmol), Pd(OAc)2 (10 mol%) in DCM (1.0 mL) was stirred at 70 °C. After the reaction was completed, the mixture was extracted with EtOAc (10 mL * 3). The organic phase was dried over Na2SO4. Then the solvent was removed under reduced pressure to provide the crude product. The purification was performed by flash column chromatography on silica gel. |
75% | With oxygen; palladium diacetate; eosin y In chlorobenzene at 20℃; for 15h; Irradiation; | |
With palladium diacetate In 1,2-dichloro-ethane at 20℃; for 10h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With di-μ-chloro-bis[chloro(η5-pentamethylcyclopentadienyl)cobalt]; silver(I) triflimide In 1,2-dichloro-ethane at 130℃; for 16h; Sealed tube; | |
76% | With silver hexafluoroantimonate; boron trifluoride diethyl etherate; [CoCp*(CO)I2]; iron(II) acetate In 1,2-dichloro-ethane at 135℃; for 12h; Inert atmosphere; | |
76% | Stage #1: N-(4-chlorophenyl)acetamide With 2,6-dichloropyridine; trifluoromethylsulfonic anhydride In 1,2-dichloro-ethane at -78 - 0℃; for 0.416667h; Inert atmosphere; Stage #2: diphenyl acetylene In dichloromethane; 1,2-dichloro-ethane at 90℃; for 14h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With chloro-trimethyl-silane; potassium iodide at 110℃; for 0.25h; Microwave irradiation; | General Procedure for acetylation: General procedure: TMSCl (0.1 mL, 0.8 mmol) and KI (132 mg, 0.8 mmol) was dissolved in CH3CN (2 mL) in a 10 mL microwave reaction vial. The mixture was allowed to stir for 15 min when a deep yellow color generated. The amine (4 mmol) dissolved in CH3CN (4 mL) was added. Sealed with a Teflon septum, the mixture was heated under microwave for 15 minutes at 110 °C. After cooling, CH3CN was removed in vacuum. The mixture was extracted with ethyl acetate (2 × 20 mL) and the combined organic layer was washed with water, sodium thiosulphate, sodium bicarbonate, and brine. Drying over Na2SO4 and removal of the solvent under reduced pressure, produced the crude mixture which was purified by column chromatography. |
68% | Stage #1: 4-chloro-aniline 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. |
53% | 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. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With tetrabutylammonium tetrafluoroborate In ethyl acetate at 20℃; for 24h; Electrochemical reaction; | |
78% | With tris(2,2'-bipyridyl)ruthenium dichloride In acetonitrile at 20℃; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate In water at 80℃; for 5.66667h; 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 |
---|---|---|
90% | With silver(I) acetate; palladium diacetate; trifluoroacetic acid at 120℃; for 24h; Sealed tube; Inert atmosphere; Schlenk technique; | Oxindoles 3 from Anilides 1 and Ethyl 2-Iodoacetate (2a); General Procedure 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 |
---|---|---|
79% | With silver(I) acetate; palladium diacetate; trifluoroacetic acid at 120℃; for 24h; Sealed tube; Inert atmosphere; Schlenk technique; | Phenanthridones 6 from Anilides 1 and 2-Iodobenzoates 5; General Procedure General procedure: A seal-tube (15 mL) initially fitted with a septum containing anilide 1 (0.5 mmol), Pd(OAc)2 (11.3 mg, 0.050 mmol, 10 mol%), and AgOAc (83.5 mg, 0.50 mmol) was evacuated and purged with N2 three times. TFA (4.0 mL) and 2-iodobenzoate 5 (0.75 mmol) were added to the system and the reaction mixture was stirred at 120 °C for 24 h. The reaction mixture was cooled to r.t. and filtered through a short Celite pad and washed with CH2Cl2 several times. The filtrate was concentrated by vacuum and purified on a silica gel column using hexane/EtOAc as eluent to give the corresponding pure phenanthridone product 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tetra-n-butylphosphonium acetate In tetrahydrofuran at 25℃; for 12h; | Typical Procedure for the Preparation of 4 and 6 General procedure: To a stirred solution of amide (1.5 mmol), propiolate (1.0mmol), and TBPA (20 mol%) in THF (3 mL), the N-heterocycle(1.0 mmol) was added slowly at 25 °C (for 10 min), and theresulting mixture was stirred at ambient temperature for 12 h.After completion of the reaction (monitored by TLC), themixture was evaporated in vacuo followed by addition of H2O(10 mL), and the pH was adjusted to 2 using concentrated HCl.Afterwards, CH2Cl2 (5 mL) was added, the mixture was stirredfor an additional 30 min, and two layers were separated. Theaqueous layer was extracted with CH2Cl2 (3 × 10 mL), the combinedorganic layers were dried over MgSO4, filtered, and concentratedin vacuo to yield the crude product (purity 75-82%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: N-(4-chlorophenyl)acetamide With iodine; triethylamine; triphenylphosphine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: diethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; | General procedure for the synthesis of substituted amidines General procedure: To a solution of Ph3P (0.415 mmol) in dichloromethane (2 mL) was added I2 (0.415 mmol) at 0 °C under N2. The resulting solution was subsequently added with amide (0.277 mmol), followed by triethylamine (1.385 mmol) at 0 °C and continueously stirred at this temperature for 30 min. After that, an amine (0.332 mmol) was added to the mixture and the solution was allowed to warm up to room temperature and stirred until completion of the reaction. The crude material was purified by column chromatography using ethyl acetate/hexanes as the eluent to afford pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In ethyl acetate at 30 - 85℃; for 4.5h; | 3 example 3 A reaction vessel equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel was charged with 0.09 mol of 2-amino-5-chloro-benzophenone (2) in an amount of 350 ml of an 85% ethyl acetate solution, Stirring speed 160rpm, solution temperature 30 , dropping p-chloroacetanilide 0.11mol, added slowly after heating, the solution temperature maintained at 85 , reaction time 4.5h, and then reduce the solution temperature to 8 , the precipitation of yellow crystals, pumping Filtration, mass fraction of 75% ethylenediamine washing, potassium bromide solution washing, activated alumina dehydration, 2-chloro-acetyl-5-chloro-benzophenone 25.78g, yield 93%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | 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 |
---|---|---|
98% | With potassium <i>tert</i>-butylate at 130℃; for 0.5h; Inert atmosphere; Microwave irradiation; | |
84% | With Imidazole hydrochloride at 150℃; for 4h; Sealed tube; | 3.2. General Procedures for the Synthesis of N-Acetamides 1a-1w General procedure: To a mixture of aromatic or aliphatic or heterocyclic amine (3.0 mmol, 1.0 equiv.), Imidazolium chloride (1.0 mmol, 0.3 equiv.), N,N-Dimethyl acetamide (2.0 mL) was added. The mixture was refluxed at 150 °C and the progress of the reaction was monitored by TLC visualized with UV short wavelength followed by iodine stain. After completion, the mixture was diluted with cold water(10 mL) then extracted with EtOAc (10 mL). The EtOAc layer was washed with 1 M hydrochloric acid (3.0 15 mL). Adsorption of pigment with activated carbon, filtration of filtrate. The filtrate was dried over anhydrous Na2SO4 and concentrated under vacuum to obtain crude N-acetamide amine, the N-acetamide amine product was isolated by column chromatography eluting with petroleum ether:ethyl acetate (10:1) mixtures. |
84% | With 10 wt. % sulfated polyborate In neat (no solvent) at 120℃; for 6h; Green chemistry; | Representative procedure for transamidation of carboxamides General procedure: A mixture of amine (2.0 mmol), carboxamide (2.4 mmol) and sulfated polyborate (10 wt.%) was heated at 120° C. The reaction was monitored by thin-layer chromatography. After completion of the reaction, the mixture was cooled to room temperature and quenched with water; the precipitated solid was filtered at the vacuum pump, washed with water (3 x 5 mL), dried under vacuum and recrystallized from ethanol to afford the pure organic product. For liquid products (1g, 2e, and 3e), the reaction mixture was diluted with water and extracted with ethyl acetate (3 X 5 mL). The combined organic layers were washed with water, dried over sodium sulfate, filtered and evaporated under reduced pressure to get the crude products, which were purified by column chromatography using silica as the stationary phase and ethyl acetate/petroleum ether as the mobile phase. To recycle the catalyst, the aqueous quench and washes were saved and evaporated, then dried under vacuum. The solid thus obtained was treated as previously described43 and used in subsequent runs without significant loss of yield. |
75% | With 1H-imidazole; nickel oxinate at 150℃; | |
33% | With ammonium iodide at 125℃; for 18h; | General procedure for the synthesis of compounds 2a and 3a. General procedure: NH4I (1.0equiv., 0.5mmol, 73mg) was added to a solution of 4-methoxyaniline (1a) (0.5mmol, 62mg) in DMF (1mL). The reaction mixture was heated to 125°C and stirred for 11h. Upon reaction completion (monitored by TLC), the reaction was cooled to room temperature, diluted with saturated NH4Cl solution, and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na2SO4. After filtration and removal of the solvent in vacuo, the resulting residue was purified by flash column chromatography on silica gel (ethyl acetate/petroleum ether=1/9) to give product 2a. Compound 3a was prepared by a similar procedure using DMA as the acylation reagent promoted by 2.0equiv. NH4I. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 66% 2: 13% | With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; silver(I) hexafluorophosphate; copper diacetate In 1,2-dichloro-ethane at 80℃; for 24h; Inert atmosphere; Schlenk technique; | Olefination of acetanilide General procedure: In a carius tube, acetanilide (27 mg, 0.2 mmol), [Cp*IrCl2]2 (5 mg, 0.006 mmol), AgPF6 (10 mg, 0.04 mmol) and Cu(OAc)2 (75 mg, 0.4 mmol) were dissolved in DCE (3 mL). To this suspension was added methyl acrylate (28 µL, 0.3 mmol) and the mixture degassed (3xfpt). It was then heated at 80 °C for 24 h, filtered through celite, and the solvent evaporated to give the crude product which was purified by column chromatography on silica gel using ethylacetate/hexane (2:3, v/v) as eluent. A similar procedure was used for the other acetanilides, acetophenones and benzamides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With dmap; tributylphosphine In toluene at 110℃; for 20h; Inert atmosphere; | General Procedure for ruthenium catalyzed selective cleavage of the N-propargyl group from sulfonamides and amides General procedure: A mixture of N-propargyl aniline derivatives (0.1 mmol), [Ru(C8H12)Cl2]n (10 mol%), tributyl-phosphane (6 mol%), DMAP (4 mol% ) in toluene (1 mL) was heated to 110 °C under nitrogen atmosphere. The resulting mixture was stirred vigorously for 20 h. After completion of the reaction, the mixture was purified by flash chromatography on silica gel to give the desired product in 10~95% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With (1S)-10-camphorsulfonic acid; palladium diacetate; Selectfluor In acetone at 20℃; for 7h; regioselective reaction; | 10 4.2. General procedure A: procedure for the arylation reactions General procedure: A solution of Anilide, arene, Selectfluor, Pd(OAc)2, D-CSA in solvent was stirred at room temperature. After the reaction was completed, the mixture was extracted with EtOAc (10 mL * 3). The organic phase was dried over Na2SO4. Then the solvent was removed under reduced pressure to provide the crude product. The purification was performed by flash column chromatography on silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With silver hexafluoroantimonate; carbonyl(pentamethylcyclopentadienyl)cobalt diiodide; sodium acetate In 1,2-dichloro-ethane at 80℃; for 24h; Sealed tube; regioselective reaction; | Typical reaction protocol for alkylation General procedure: The experimental alkylation procedure is similar to that as described in [18]. A screw top vial, under air, was charged with acetanilide substrate (1.0 mmol), [Cp*Co(CO)I2] (20 mol %, 0.20 mmol,95.2 mg), AgSbF6 (40 mol %, 0.4 mmol, 137.4 mg), NaOAc(40 mol %, 0.4 mmol, 16.4 mg), 3-buten-2-one (1.5 equiv,1.5 mmol, 105 mg) and 1,2-DCE (8.0 mL). The vial was sealed,and the reaction mixture heated to 80 °C with stirring for 24 hours. After this period, the solvent was removed under reduced pressure and the crude product purified by column chromatography (ethyl acetate/petroleum ether; 80:20 in most cases). For full characterisation data of all products obtained, see Supporting Information File 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: N-(4-chlorophenyl)acetamide With trichlorophosphate In dichloromethane at 20℃; for 1.5h; Inert atmosphere; Stage #2: 2-ethoxycarbonylaniline In dichloromethane at 40℃; Inert atmosphere; Stage #3: With sodium hydroxide In dichloromethane; water Inert atmosphere; | General procedure for preparation of quinazolin-4(3H)-one derivatives General procedure: A mixture of an amide (1 equivalent) in dry DCM 60 mL and POCl3 (1.26 ml, 1.36 mmol, 2 equation) was stirred for 1.5 h at room temperature. To the reaction, a solution of ethyl 2-aminobenzoate (1) (1.18 g, 0.71 mmol, 1.05 equivalent) in DCM (20 mL) was added dropwise and heated to 40°C overnight. Ice-cold water was then added followed by a 30% NaOH solution to alkaline pH. The organic solvents were concentrated under vacuum, the extracted with DCM, brine and dried over MgSO4. The solvent was evaporated in vacuum and the crude purified by chromatography on silica gel (petroleum ether/ethyl acetate) to give the desired products (11-19), (Table 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In lithium hydroxide monohydrate at 20℃; for 12h; | 5 Example 5 Under room temperature and air atmosphere, 4-chloroaniline (0.3mmol), thioacetic acid (0.45mmol), and water solvent (H2O) (1mL) were successively added to the reaction tube, and then the reaction was performed at room temperature for 12 hours. The product was isolated by column chromatography in 99% yield. |
73% | With 9-mesityl-10-methylacridin-10-ium tetrafluoroborate In acetonitrile at 20℃; for 5h; Irradiation; | |
73% | With 9-mesityl-10-methylacridin-10-ium tetrafluoroborate In acetonitrile at 20℃; for 5h; Irradiation; | 4 Example 4: Preparation of N- (4-chlorophenyl) acetamide (3d) In air, p-chloroaniline (0.2 mmol, 26 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 25 mg of a white solid product with a yield of 73%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With 1,1,1,3',3',3'-hexafluoro-propanol; 3-chloro-benzenecarboperoxoic acid In water at 40 - 80℃; | 5 Example 5. Preparation of N-(4-iodo-3-toluene)-N-4-chlorophenylacetamide Add 0.2mmol 4-chloroacetanilide, 0.3mmol 2-iodotoluene, 0.3mmol m-chloroperoxybenzoic acid, 1mL hexafluoroisopropanol and a magnet No. 5 in order, and pass condensed water through the condenser from bottom to top Afterwards, the reactor was placed in a 40-80°C oil bath for heating for 2-8 hours, 15 mL of water was added, and each time was extracted three times with 10 mL of ethyl acetate. The resulting organic phases were combined and spin-dried on a rotary evaporator. After separation and purification by column chromatography, 75.5 mg of N-(4-iodo-3-toluene)-N-4-chlorophenylacetamide was obtained, which was a pale yellow solid, and the yield was 98%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: 4-chloro(ethylbenzene) With N-hydroxyphthalimide; oxygen; cobalt(II) diacetate tetrahydrate; acetic acid In formic acid at 80℃; for 12h; Stage #2: With nitromethane; trifluoromethylsulfonic anhydride In formic acid at 80 - 120℃; | 112 Example 112 p-Chloroacetanilide Take a reaction tube, add 40-50mg (0.3mmol) of p-chloroethylbenzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate, and 0.5mL of acetic acid, and stir under an oxygen atmosphere at 80 for 12 Then add 500-600 mg (0.5 mL) of nitromethane, 150-200 mg (0.6 mmol) of trifluoromethanesulfonic anhydride, 30-60 mg (0.75 mmol) of formic acid, and stir for 1-72 hours at 80-120°C. After the reaction was completed, 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 37.5 mg of p-chloroacetanilide with a yield of 74%. |
74% | Stage #1: 4-chloro(ethylbenzene) 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 |
---|---|---|
94% | 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 |
---|---|---|
76% | With trichlorophosphate In acetonitrile at 0 - 68℃; for 16.5h; | General Procedure 5: General procedure: To a ca. 0.22 M solution of the corresponding amide (1 eq) in acetonitrile is added imidazole (12 eq) at room temperature. The reaction mixture is cooled to 0-5 °C prior to the dropwise addition of phosphorus oxychloride (2 eq). The reaction mixture is allowed to stir for 30 min at 0-5 °C. After removal of the ice bath the reaction mixture is heated to 68 °C for ca. 16 h. After cooling the reaction mixture to room temperature the solids are removed by filtration and washed with acetonitrile. The filtrate is concentrated in vacuo. The residue is partitioned between ethyl acetate and water, and the layers are separated. The aqueous layer is extracted with three portions of ethyl acetate. The combined organic layers are washed with one portion of water, one portion of saturated ammonium chloride solution, and one portion of brine. The combined organic layers are dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product is triturated with a mixture of ethyl acetate and n-heptane. The solids are collected by filtration, washed with n-hexane and dried in vacuo to give an imidazole intermediate of formula IV. |
76% | With trichlorophosphate In acetonitrile at 0 - 68℃; for 16.5h; | General Procedure 5: General procedure: To a ca. 0.22 M solution of the corresponding amide (1 eq) in acetonitrile is added imidazole (12 eq) at room temperature. The reaction mixture is cooled to 0-5 °C prior to the dropwise addition of phosphorus oxychloride (2 eq). The reaction mixture is allowed to stir for 30 min at 0-5 °C. After removal of the ice bath the reaction mixture is heated to 68 °C for ca. 16 h. After cooling the reaction mixture to room temperature the solids are removed by filtration and washed with acetonitrile. The filtrate is concentrated in vacuo. The residue is partitioned between ethyl acetate and water, and the layers are separated. The aqueous layer is extracted with three portions of ethyl acetate. The combined organic layers are washed with one portion of water, one portion of saturated ammonium chloride solution, and one portion of brine. The combined organic layers are dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product is triturated with a mixture of ethyl acetate and n-heptane. The solids are collected by filtration, washed with n-hexane and dried in vacuo to give an imidazole intermediate of formula IV. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | 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 |
---|---|---|
86% | In ethanol at 20℃; for 6h; Schlenk technique; Irradiation; Green chemistry; | 5 Example 5 In a 25 mL Schlenk tube, amine 1e (0.2 mmol, 25.4 mg), 2,3-butanedione (1.2 mmol, 103.3 mg), ethanol (95%, 0.5 mL) were added sequentially in a 25 mL Schlenk tube, and then after 6 hours of routine stirring under 40W white LED irradiation, the reaction system was quenched with saturated sodium sulfite solution, extracted with ethyl acetate 3 times, combined with the organic layer, and dried with anhydrous sodium sulfate. The solvent and silica gel adsorption were removed by rotary evaporator, and the product 3e could be obtained by simple column chromatography, and the yield was 86%. The main test data of the prepared products are as follows, and through the analysis, it can be seen that the actual synthetic products are consistent with the theoretical analysis. |
Tags: 539-03-7 synthesis path| 539-03-7 SDS| 539-03-7 COA| 539-03-7 purity| 539-03-7 application| 539-03-7 NMR| 539-03-7 COA| 539-03-7 structure
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