| 91% |
With indium(III) chloride In benzene for 24h; Reflux; |
|
| 91% |
With cerium(III) chloride In ethyl acetate at 50℃; for 6h; |
|
| 91% |
With N,N,N-triethyl-N-sulfoethanammonium chloride In neat (no solvent) at 80℃; for 1.5h; |
|
| 90% |
With zinc(II) oxide at 110℃; for 3h; |
|
| 90% |
With Amberlyst 15 In toluene for 12h; Molecular sieve; Reflux; Dean-Stark; |
|
| 90% |
With silica-supported iron oxide In toluene at 100℃; for 1h; Schlenk technique; Inert atmosphere; |
2.2.4. General procedure for the synthesis of products
General procedure: To a Schlenk tube filled with Fe3O4(at)MCM (15 mg) andtoluene (0.5 mL), aldehyde (0.12 mmol) and p-toluenesulfonamide(17.12 mg, 0.1 mmol) were added under nitrogen atmosphere. The reaction mixture was stirred for1 h at 100 °C. Then, the silica-coated magnetic nanoparticleswere separated using a simple magnet. The solutionof the reaction-separated systemwas transferred into around-bottomed flask. After the organic phase was evaporatedunder reduced pressure, the obtained crude productwas purified by recrystallization from ethyl acetate and nhexane,affording the pure product in high yield (up to98%). |
| 89% |
With 3-methyl-1-sulphonic acid imidazolium chloride at 20℃; for 0.5h; Ionic liquid; |
|
| 87% |
Stage #1: 4-methyl-benzaldehyde; toluene-4-sulfonamide In toluene for 1h;
Stage #2: With boron trifluoride diethyl etherate In toluene for 4h; Reflux; |
1. Synthetic procedure for five substrates: 4-methyl-N-phenylmethylene-benzenesulfonamide (1a), 4-methyl-N-[(2,4,6-trimethylphenyl)methylene]-benzenesulfonamide (1b), 4-methyl-N-[(3,4-dimethylphenyl)methylene]- benzenesulfonamide (1c), 4-methyl-N-[(4-methylphenyl)methylene]- benzenesulfonamide (1d), and 4-methyl-N-[4-(1-methylethyl)phenyl]methylene}-benzenesulfonamide (1e).
General procedure: 4-methyl-benzenesulfonamide (12 mmol) was added to a mixture of toluene (25 mL) and benzaldehyde (10 mmol) in a 50 mL flask. After stirring for 1h, the mixture was kept heating and BF3OEt2 (2 mmol) was added very slowly. When the reaction completed (as monitored by TLC), the reaction solution was quenched with NaOH solution (1 M) and extracted with ethyl acetate for three times. The combined organic layers were washed several times with brine, dried over anhydrous Na2SO4, and concentrated under reduced atmosphere to obtain the primary product. In some cases, this primary product was purified using flash column chromatography to afford pure substrate 1a. |
| 85% |
With boron trifluoride diethyl etherate In toluene Dean-Stark; Reflux; |
|
| 80% |
With Amberlyst(R) 15 ion-exchange resin In toluene for 16h; Inert atmosphere; Reflux; Molecular sieve; |
General method B: Synthesis for tosyl aldimines.
General procedure: The aryl aldehyde (11.68 mmol) was added to a stirred mixture of 4-methylbenzenesulfonamide (1.00 g, 5.84 mmol), 4 Å molecular sieves (5.00 g, 5.84 mmol) and Amberlyst(R) 15 ion-exchange resin (0.37 g, 1.17 mmol) in toluene (10 mL) at 20 °C under nitrogen. The resulting mixture was heated to reflux and stirred at reflux for 16 hours. The mixture was cooled and filtered. The filtrate was concentrated under reduced pressure to give the crude product. Purification was by recrystallisation from EtOAc and heptane mixtures to give the tosyl aldimine products. |
| 77% |
With pyrrolidine In dichloromethane at 60℃; Molecular sieve; Sealed tube; |
|
| 76% |
With tetrabutylammomium bromide; magnesium oxide at 110℃; for 0.2h; Microwave irradiation; neat (no solvent); |
|
| 71% |
With tetrachlorosilane at 120℃; for 3h; |
|
| 71% |
With [bis(acetoxy)iodo]benzene; iodine at 50℃; for 24h; Inert atmosphere; |
4.2.1. General Procedure for the Preparation of N-Sulfonyl Imines (2) (1H-NMR Yields)
General procedure: To an oven-dried reaction tube was added aldehyde (1.25 mmol, 5 equivalents), PhI(OAc)2(0.50 mmol, 2 equivalents), sulfonamide (0.25 mmol, 1 equivalent), I2 (0.25 mmol, 1 equivalents),and CDCl3 (3 mL). The mixture was stirred at 50 °C under argon for 24 h. After 24 h, the reaction wascooled to room temperature and an internal standard was added (1,4-dimethoxybenzene, 0.25 mmol,35 mg); the mixture then was stirred for an additional 5-10 min. The percent yield was calculatedagainst the internal standard via 1H-NMR integrations of the imine C-H signal and the aromatic (4H)signal of the internal standard. |
| 23% |
Stage #1: 4-methyl-benzaldehyde; toluene-4-sulfonamide With formic acid; sodium benzenesulfonate In water at 20℃; for 16h;
Stage #2: With sodium hydrogencarbonate In water at 20℃; for 2h; |
|
|
With 4 A molecular sieve; amberlite H+ resin IR-120 In toluene at 120℃; for 12h; |
|
|
With toluene-4-sulfonic acid |
|
|
With titanium tetrachloride; triethylamine In dichloromethane Inert atmosphere; |
|
|
With titanium tetrachloride; triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; |
|
|
With Amberlyst 15 In toluene at 140℃; for 16h; Molecular sieve; Sealed tube; Inert atmosphere; |
|
|
In dichloromethane Inert atmosphere; Molecular sieve; Reflux; |
|
|
With tetraethoxy orthosilicate at 160℃; for 10h; |
|
|
With tetraethoxy orthosilicate Dean-Stark trap; Inert atmosphere; |
|
|
Stage #1: 4-methyl-benzaldehyde; toluene-4-sulfonamide With formic acid In water at 20℃;
Stage #2: With sodium hydrogencarbonate In dichloromethane; water at 20℃; |
|
|
With tetraethoxy orthosilicate at 160℃; for 10h; |
General procedure: N-sulfonyl imines 3a-q described in this paper were prepared by condensation of the corresponding aldehydes with p-toluenesulfonamide according to the reported procedure with minor modification:1 the aldehyde (25.0 mmol), p-toluenesulfonamide (25.0 mmol), and Si(OEt)4 (27.5 mmol, 1.1 equiv.) were combined into a flask equipped with an oil-water separator and heated at 160°C for 10 hours. The produced EtOH was collected in the oil-water separator and released it at regular intervals. After cooling down, the residues of the reaction directly recrystallized for two times with EtOAc and Hexanes. |
|
With tetraethoxy orthosilicate at 160℃; for 6h; Inert atmosphere; |
2.3 Synthesis of N-Ts aldimins 2
Representative procedure: a mixture of benzaldehyde (3.7 g, 36.7 mmol), p-toluenesulfonamide (6.3 g, 36.7 mmol) and tetraethyl orthosilicate (8.0 g, 38.6 mmol) was heated at 160 °C for 6 hours. After cooling to room temperature, the mixture was purified by recrystallization from ethyl acetate/hexane or ether/hexane, N-benzylidene-4-methylbenzenesulfonamide (2a) was obtained as a white solid. The other aldimines 2b-h were prepared analogously. |
|
With Amberlyst-15 In toluene for 14h; Molecular sieve; Dean-Stark; Reflux; |
|
|
With toluene-4-sulfonic acid In toluene at 150℃; for 24h; Inert atmosphere; |
|
|
With amberlite H+ resin IR-120 In toluene at 120℃; for 12h; Dean-Stark; Molecular sieve; |
1.1. General procedure for the synthesis of N-sulfonyl aldimines (1a, 1e-k)1
General procedure: A solution of the aldehyde (17 mmol) in toluene (70 mL) was placed in a round bottomed flask equipped with a Dean Stark assembly. p-Toluenesulfonamide/benzenesulfonamide (18 mmol), amberlite H+ resin IR-120 (2 g) and powdered molecular sieves (4 Å, 2 g) were added to the reaction flask and the mixture was stirred at 120 °C for 12 h, with azeotropic removal of water. After the reaction was complete (based upon the theoretical amount of water removal, and monitoring reaction by TLC), the mixture was allowed to cool at room temperature and filtered. The solvent was removed under reduced pressure and the resulting N-sulfonyl aldimines (1a, 1e-k) were further purified by crystallization from n-hexane. |
|
With tetraethoxy orthosilicate |
|
|
With formic acid; sodium benzenesulfonate In water at 20℃; for 16h; |
|
|
With bromobenzene; zinc In tetrahydrofuran Reflux; |
General procedure for the homopropargylic N-sulfonylamides formation
General procedure: A round-bottom flask fitted with activated zinc powder (260 mg, 4 mmol) and anhydrous THF (3 mL). Benzyl bromide (0.24 mL, 2 mmol) was added. After stirred at room temperature for 30 min, p-toluenesulfonamide (171 mg, 1 mmol) and aldehyde (1.1 mmol) were successively added. The reaction mixture was stirred at reflux until the amide disappeared monitored by TLC. Then the mixture was cooled to room temperature, and propargyl bromide (0.117 mL, 1.5 mmol) was added dropwise. The reaction was stirred at room temperature until the imide disappeared monitored by TLC. The mixture was quenched with brine, and extracted by ethyl acetate (50mL×3). The organic layer was dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel to provide the desired product. |
|
With tetraethoxy orthosilicate at 160℃; for 6h; Inert atmosphere; |
|
|
With tetraethoxy orthosilicate |
|
|
With magnesium sulfate; acetic acid In water; toluene |
|
|
With toluene-4-sulfonic acid In toluene for 8h; Reflux; |
|
|
With iron(III) chloride In dichloromethane at 40℃; for 1h; Green chemistry; |
|
|
With tetraethoxy orthosilicate at 160℃; for 5h; Inert atmosphere; Schlenk technique; |
|
|
With formic acid; sodium 4-methylbenzenesulfinate In water at 20℃; for 12h; |
|
|
With tetraethoxy orthosilicate at 140 - 160℃; Inert atmosphere; |
|
|
In toluene at 150℃; for 72h; Dean-Stark; |
Procedure of the Preparation of N-Tosylbenzaldimine
General procedure: p-Toluenesulfonamide (4.5 g, 26.3 mmol) and benzaldehyde (2.4 mL, 26.3 mmol) were mixed via syringe in toluene (70 mL). The mixture was heated to reflux with a Dean-Stark trap at 150 °C for 72 hrs until the reaction completed as monitored by TLC. After the solution was cooled down, the reaction mixture was concentrated under reduced pressure and the compound was recrystallized from diethyl ether to give the pure imine as white solid. (6.16 g, yield 90%). |
|
With boron trifluoride diethyl etherate In toluene Reflux; |
2.3.1. Typical procedure for synthesis of N-tosyl aldimines precursors
General procedure: All solvents were purified by distillation method. Other reagentswere used as received. Thin layer chromatography (TLC) was carriedout using Merck 0.2 mm silica gel 60 F-254 Al-plates (200-300 mesh).Typically, 4-methyl-benzenesulfonamide (12 mmol) was added to amixture of toluene (25 mL) and benzaldehyde (10 mmol) in a 50 mLflask. After stirring for 1 h, the mixture was kept heating and BF3OEt2(2 mmol) was added slowly. When the reaction completed, the reactionsolution was quenched with NaOH solution (1 M) and extracted withethyl acetate for three times. The organic layers were washed severaltimes with brine, dried over anhydrous Na2SO4, and concentrated toobtain the primary product. In some cases, this primary product waspurified using flash column chromatography to afford pure substrate 4-methyl-N-phenylmethylene-benzenesulfonamide (1a) (Scheme 1). |
|
With tetraethoxy orthosilicate at 160℃; |
General procedure for preparation of N-sulfonyl imines (2)
General procedure: N-sulfonyl imines 2 were prepared according to the literature procedures.2 A mixture of aldehyde (1.0 eq.), p-toluenesufonamide (1.0 eq.) and tetraethoxysilane (1.05 eq.) was heated at 160 °C for 4-6 h, and then cooled to room temperature. The resulting mixture was crystallized with ethyl acetate and hexane (10:1 to 1:1) and the resulting solid was collected by filtration, dried in vacuum to afford N-sulfonylimines 2. |
|
With tetraethoxy orthosilicate at 160℃; for 4h; Inert atmosphere; |
|
|
With titanium(IV) tetraethanolate In toluene at 150℃; for 12h; |
|
|
With tetraethoxy orthosilicate at 160℃; |
|
|
With boron trifluoride diethyl etherate In toluene Reflux; Inert atmosphere; Dean-Stark; |
|
|
With boron trifluoride diethyl etherate In toluene at 110℃; |
|
|
With pyrrolidine In dichloromethane at 60℃; for 20h; Inert atmosphere; Molecular sieve; Schlenk technique; |
Synthesis of N-tosylaziridinedicarboxylate substrates 1a-1n
General procedure: Under argon atmosphere, the corresponding aromatic aldehyde (10 mmol, 1 equiv.), pyrrolidine (1 mmol, 0.1 equiv.) and 4Å molecular sieves (10g, 1g/mmol) were added into a solution of R1NH2 (10 mmol, 1 equiv.) in CH2Cl2 (30 mL). The mixture was stirred in a 100 mL Schlenk tube at 60 C for 20 h. Then, cooled to roon temperature, and the reaction mixture was filtered through a short pad of silica gel or Celite. The filtrate was concentrated in vacuo to get S-1a. Under argon atmosphere, NaH (11 mmol, 60% dispersion in mineral oil, 1.1 equiv) was added into solution of S-1a (10 mmol, 1 equiv.), 2-bromomalonate (11 mmol, 1.1 equiv.) in 20 mL of dry CH3CN was cooled to 0 oC. The resulting mixture was warmed up and stirred at room temperature. Upon completion (monitored by TLC), the reaction mixture was filtered through a small plug of silica gel eluted with CH2Cl2 to remove the excess NaH and resulting NaBr. After concentration in vacuo, the crude mixture was quickly purified by flash chromatography on silica gel (eluent: n-Hexane/EtOAc = 100/2 to 100/15) to afford the desired product 1a. |
|
With tetraethoxy orthosilicate at 160℃; for 6h; Dean-Stark; Inert atmosphere; |
|
|
With tetraethoxy orthosilicate at 120℃; |
|
|
With tetraethoxy orthosilicate In neat (no solvent) at 140℃; Dean-Stark; Inert atmosphere; |
|
|
In ethanol at 80℃; |
2.1.1 General procedure for the synthesis of N-[(R-phenyl)methylidene]-4-methylbenzenesulfonamide 3 (a-t) [28]
General procedure: An equimolar quantity of corresponding aromatic aldehyde 2 (a-t) (0.01mol) and 4-methylbenzenesulfonamide (1) (1.12g, 0.01mol) in the presence of 20ml of absolute ethanol was refluxed for 5-6h. The completion of the reaction was ascertained by TLC (carbon tetrachloride/methanol, 2:1). The whole reaction mixture was transferred into a beaker containing crushed ice in boiling condition and filtered after attaining room temperature. Then the product was kept overnight, dried, and recrystallized using ethanol to get corresponding pure N-[(R-phenyl)methylidene]-4-methylbenzenesulfonamide derivatives 3 (a-t). |
|
With boron trifluoride diethyl etherate In toluene at 120℃; for 12h; Inert atmosphere; Sealed tube; |
|
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