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Synthesis of N-Sulfenylimines from Disulfides and Primary Methanamines
Robert Kawȩcki ;
Abstract: N-Sulfenylimines (sulfenimines, thiooximes, N-alkylidenesulfenamides) were efficiently synthesized through the reaction of primary amines and disulfides with NBS or bromine. This reaction can be carried out in an open flask at room temperature without the need for any transition-metal-containing additives. The use of thiols instead of disulfides gave similar results. A wide range of amines were reacted with aryl and alkyldisulfides, resulting in the formation of sulfenimines in a yield of 44–99%.
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CAS No. : | 91-00-9 |
Formula : | C13H13N |
M.W : | 183.25 |
SMILES Code : | NC(C1=CC=CC=C1)C2=CC=CC=C2 |
MDL No. : | MFCD00008059 |
InChI Key : | MGHPNCMVUAKAIE-UHFFFAOYSA-N |
Pubchem ID : | 7036 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
75% | With potassium carbonate In methanol; water; toluene | EXAMPLE 1 N-Benzhydrylazetidine To A solution of 6.9 kg (50 moles) of potassium carbonate in 7.5 liters of water was added 18.5 liters of 1-butanol, 7.85 kg (50 moles) of 1-bromo-3-chloropropane and 5.18 kg (25 moles) of benzhydrylamine (97percent purity with 10percent toluene as a residual solvent). The reaction mixture was heated to 100° C. externally with steam and stirred slowly under a nitrogen gas atmosphere overnight. About 12 liters of water was added to the mixture to dissolve some inorganic salt precipitate. The layers were separated and organic layer was distilled under reduced pressure to remove about 18 liters of butanol and water. To the residue was added 1.5 liters of methanol and the resulting mixture was stirred slowly while cooling down to room temperature. The white solid was collected by filtration, rinsed twice with 700 ml portions of methanol and dried in a vacuum oven to give 4.2 kg (75percent) of product, m.p. 107°-109° |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; | (Diphenylmethyl)[(4-chloro-3-nitrophenyl)sulfonyl]amine. To a stirred solution of aminodiphenylmethane (1.9 g, 11 mmol) and 4-chloro-3-nitrobenzenesulfonyl chloride (2.56 g, 10 mmol) in 75 mL of dichloromethane was added triethylamine (2 mL, 14.4 mmol). The solution was stirred for 16 h. The reaction mixture was washed successively with 1M HCl and brine. The organic layer was dried over MgSO4, filtered and evaporated. The resulting yellow solid was recrystallized from ethyl acetate/hexane to give 2.98 g of product in (74%) yield as pale yellow crystals: 1H NMR (400 MHz, CDCl3) delta5.34 (d, 1H, J=7.0 Hz), 5.73 (d, 1H, J=7.0 Hz), 7.11-7.14 (m, 4H), 7.23-7.26 (m, 6H), 7.43 (d, 1H, J=8.5 Hz), 7.67 (dd, 1H, J=2.0, 8.5 Hz), 7.93 (d, 1H, J=2.0 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In hexane; water; ethyl acetate; N,N-dimethyl-formamide; | PREPARATION 9 N-(Diphenylmethyl)-1H-imidazole-4-carboxamide A mixture of 11.7 g of 4-imidazolecarboxylic acid, 18.7 g of 1,1'-carbonyldiidmidazole, 20 ml of diisopropylethylamine and 600 ml of DMF was heated at 35° C. for approximately 18 hours. Twenty milliters of aminodiphenylmethane were added and the solution stirred at 35° C. for approximately 21/2 days. The mixture was concentrated in vacuo and the residue added to 400 ml of water. The mixture was extracted with ethyl acetate and the organic layer was washed with a saturated sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. Two crystallizations from hot ethyl acetate/hexane provided 11 grams of the desired titled intermediate, m.p. 201°-202° C. Analysis for C17 H15 N3 O: Calc.: C, 73.63; H, 5.45; N, 15.15; Found: C, 73.90; H, 5.58; N, 15.12. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; | <strong>[866777-98-2]N-methyl-N-[(S)-2-oxiran-2-ylmethyl]methanesulfonamide</strong> is dissolved in ethanol and benzyl amine (1-1.1 equiv) is added to the solution. (Alternatively, <strong>[866777-98-2]N-methyl-N-[(S)-2-oxiran-2-ylmethyl]methanesulfonamide</strong> is dissolved in ethanol and 1,1-diphenyl-methanamine (1-1.1 equiv) is added to the solution.) The mixture is refluxed until completion of the reaction. The product is isolated and extracted. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40 mg (22%) | Example 60 N-Benzhydryl-6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-amine Hydrochloride N-Benzhydryl-6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-amine hydrochloride was prepared from <strong>[59514-18-0]6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-one</strong> (100 mg, 0.38 mmol) and benzhydrylamine (70 mg, 0.38 mmol) in a similar manner as described above to give 40 mg (22%) of a white solid; 1H-NMR (DMSO-d6): delta 11.97 (s, 1H), 10.51-10.46 (m, 1H), 10.14-10.11 (m, 1H), 7.97 (d, 2H), 7.86 (d, 2H), 7.65 (s, 1H), 7.48-7.31 (m, 7H), 7.24 (d, 1H), 5.97-5.94 (m, 1H), 4.42-4.38 (m, 1H), 2.63-2.61 (m, 2H), 2.17-1.97 (m, 3H), 1.75-1.66 (m, 1H); MS m/z (M-1) 429, 431. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In acetonitrile; at 70℃; | General procedure: A mixture of benzhydrylamine (0.50 mol), CH3CN (838 mL), 2-(2-thienyl)ethyl toluene-p-sulfonate 6a (0.50 mol) and Na2CO3 (0.91 mol) was heatedto 70 °C. After completion of the reaction, the reaction mixture was cooled,filtered and evaporated in vacuo. The residue was dissolved in benzene(1.03 L) and stirred at room temperature for 10 min, under a stream of N2,and then portions of DDQ (1.09 mol) were added over 10 min with stirring.The reaction mixture was heated under reflux for 5 h, evaporated in vacuoand treated with H2SO4 (1.40 M, 885 mL) at room temperature. Aftercompletion of the hydrolysis, the aqueous phase was extracted with CH2Cl2,followed by separation of organic and aqueous layers. The aqueous phasewas adjusted to a basic pH by sodium hydroxide solution (40percent), extractedwith CH2Cl2 and then the organic phase was distilled under reducedpressure to yield the expected product 9a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48.1% | 2.1 g of compound 1 was dissolved into 15mL of DMF, add 1.39 g of potassium carbonate, stir at 50 C with heating, add the drops of chlorotoluene (1.27g), heat to reflux, and react for 3 h, and then cool at 60 C, added the drops of Diphenyl methylamine (1.83g), heat again to reflux, carry on reaction for 1.5h, after the reaction, filter, filter cake washed with a small amount of DMF, the filtrate is distilled off under reduced pressure, add 15 g of ice water, stir, and filter and obtained a crude product, adding the crude product to methanol and then, it is made into salt with concentrated hydrochloric acid, by filter obtained hydrochloride salt of compound I-1, hydrochloride added into 6mL of water, adjust adjusting the pH at 8 with ammonia hydroxide and obtain a large amount of white powder, filter, dry, i.e. obtained Compound I-1 (2.15g, yield 48.1%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44.9% | 2.1 g of compound 1 was dissolved into 15mL of DMF, add 1.39 g of potassium carbonate, stir at 50 C with heating, add the drops of alpha-chloroethylbenzene (1.41g), heat to reflux, and react for 3h, and then cool at 60 C, added the drops of Diphenyl methylamine (1.83g), heat again to reflux, carry on reaction for 1.5h, after the reaction, filter, filter cake washed with a small amount of DMF, the filtrate is distilled off under reduced pressure, add 15g of ice water, stir, and filter and obtained a crude product, adding the crude product to methanol and then, it is made into salt with concentrated hydrochloric acid, by filter obtained hydrochloride salt of compound I-2, hydrochloride added into 6mL of water, adjust adjusting the pH at 8 with ammonium hydroxide and obtain a large amount of white powder, filter, dry, i.e. obtained Compound I-2 (2.07g, yield 44.9%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.3% | 2.1 g of compound 1 was dissolved into 15mL of DMF, add 1.39 g of potassium carbonate, stir at 50 C with heating, add the drops of 3-phenylpropyl chloride (1.55g), heat to reflux, and react for 2h, and then cool at 60 C, added the drops of Diphenyl methylamine (1.83g), heat again to reflux, carry on reaction for 1.5h, after the reaction, filter, filter cake washed with a small amount of DMF, the filtrate is distilled off under reduced pressure, add 15g of ice water, stir, and filter and obtained a crude product, adding the crude product to methanol and then, it is made into salt with concentrated hydrochloric acid, by filter obtained hydrochloride salt of compound I-3, hydrochloride added into 6mL of water, adjust adjusting the pH at 8 with ammonium hydroxide and obtain a large amount of white powder, filter, dry, i.e. obtained Compound I-3 (3.34g, yield is 70.3%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | With acetic acid; In toluene; at 100.0℃; for 26.5h;Molecular sieve; | Molecular sieve 4A (5.00 g) was put into a four-necked eggplant flask (100 mL), and dried under reduced pressure at 100 C. for 30 min, and the reaction system was purged with nitrogen. The flask was cooled to room temperature, toluene (30 mL), <strong>[1261080-59-4]methyl 2-acetyl-5-thiazolecarboxylate</strong> (5.00 g), benzhydrylamine (4.90 mL) and acetic acid (0.31 mL) were added thereto, and the mixture was stirred at the internal temperature of 100 C. for 22 hr. 4 hr after the beginning of the stirring, additional benzhydrylamine (0.70 mL) was added thereto. The reaction mixture was cooled to 70 C., and filtered using Hirsch funnel, and the filtrate was concentrated under reduced pressure to give an oil. To the residue was added a mixed solvent (30 mL) of normal hexane:toluene=2:1, cooled to -78 C., warmed to -20 C., and stirred for 1 hr. The resulting solid was collected by filtration, washed with a mixed solvent (20 mL) of normal hexane:toluene=2:1, which was cooled to -20 C., and dried under reduced pressure at 40 C. to give the title compound (4.78 g, yield 51%) as a pale-brown solid. The residual filtrate was concentrated under reduced pressure, and the residue was recrystallizd from a mixed solvent of normal hexane:toluene=6:1 (14 mL) at 0 C. The resulting solid was collected by filtration, washed with a mixed solvent of normal hexane:toluene=10:1, which was cooled to 0 C., and dried under reduced pressure at 40 C. to give the title compound (2.51 g, yield 26%) as a pale-brown solid. 1H NMR (CDCl3) δ 2.44 (s, 3H), 3.92 (s, 3H), 5.88 (s, 1H), 7.23 (t, J=7.5 Hz, 2H), 7.32 (t, J=7.5 Hz, 4H), 7.44 (d, J=7.5 Hz, 4H), 8.39 (s, 1H); 13C NMR (CDCl3) δ 14.73, 52.49, 68.59, 127.14, 127.35, 128.60, 131.41, 143.55, 148.62, 160.55, 161.94, 176.52. |
Tags: 4-Phenylbenzylamine | Amines | Aryls | Organic Building Blocks | 91-00-9
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