* 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.
A cooled solution of 4'-aminoacetophenon (10 mmol) in pyridine (10 mL) at 0 °C was treated with METHANESULFONYL chloride (15 mmol) and stirred at room temperature for 2 h. The reaction mixture was diluted with HZ0 and extracted with EtOAc several times. The combined organic layers were washed with H20 and brine, dried over MGS04, filtered, and the filtrate was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel using EtOAc: hexanes to afford 4'- (Methylsulfonylamino) acetophenone (13-5, LJO-298). 95percent yield, mp = 161 °C 1H NMR (CDC13) 8 7.97 (dd, 2 H, J= 2,6. 8 Hz, ), 7.26 (dd, 2 H, J= 2, 6.8 Hz), 6. 87 (bs, 1 H), 3.10 (s, 3 H), 2.59 (s, 3 H)
66%
With pyridine In tetrahydrofuran at 20℃; for 12 h;
General procedure: To a solution of 4-aminoacetophenone (0.68g, 5mmol) and pyridine (1.6mL, 20mmol) in THF (10mL) was slowly added the substituted sulfonyl chloride (5mmol). The reaction mixture was stirred at room temperature for 12h. Water (50mL) was added and the mixture was extracted with ethyl acetate (10mL×3), the combined organic phase was washed with 1N hydrochloric acid (30mL×2) and water (30mL×2), dried over anhydrous Na2SO4 and concentrated under vacuum to afford the product.
Reference：
[1] Journal of Enzyme Inhibition and Medicinal Chemistry, 2014, vol. 29, # 6, p. 846 - 867
[2] Organic Process Research and Development, 1998, vol. 2, # 2, p. 71 - 77
[3] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 18, p. 6043 - 6053
[4] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 12, p. 2685 - 2688
[5] Patent: WO2005/3084, 2005, A1, . Location in patent: Page 79
[6] Journal of Organic Chemistry, 1987, vol. 52, # 19, p. 4377 - 4379
[7] Journal of Organic Chemistry, 2001, vol. 66, # 25, p. 8293 - 8296
[8] Journal of the American Chemical Society, 2015, vol. 137, # 11, p. 3731 - 3734
[9] Arkivoc, 2016, vol. 2016, # 4, p. 227 - 245
[10] Asian Journal of Chemistry, 2012, vol. 24, # 3, p. 1316 - 1318
[11] Chemistry - A European Journal, 2016, vol. 22, # 47, p. 16998 - 17005
[12] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 48 - 65
[13] Journal of medicinal chemistry, 1966, vol. 9, # 1, p. 88 - 97
[14] Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy, 1982, vol. 38, # 7, p. 791 - 796
[15] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 2, p. 1056 - 1061
[16] Synthesis, 2012, vol. 44, # 9, p. 1329 - 1338
[17] Medicinal Chemistry Research, 2014, vol. 23, # 10, p. 4383 - 4394
[18] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 12, p. 2685 - 2688
2
[ 3144-09-0 ]
[ 99-90-1 ]
[ 5317-89-5 ]
Reference：
[1] Tetrahedron Letters, 2005, vol. 46, # 43, p. 7295 - 7298
[2] Organic Letters, 2011, vol. 13, # 10, p. 2564 - 2567
[3] Green Chemistry, 2014, vol. 16, # 3, p. 1480 - 1488
3
[ 99-92-3 ]
[ 7143-01-3 ]
[ 5317-89-5 ]
Reference：
[1] Patent: US2003/153596, 2003, A1,
4
[ 1197-22-4 ]
[ 108-24-7 ]
[ 5317-89-5 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 7, p. 1751 - 1755
5
[ 367-27-1 ]
[ 5317-89-5 ]
Reference：
[1] Organic Process Research and Development, 1998, vol. 2, # 2, p. 71 - 77
With pyridine; In dichloromethane; at 0 - 20℃; for 16h;
To a 0C solution of aniline (1 equiv) and pyridine (1.1 equiv) in CH2CI2 (0.35 M) was added methanesulfonyl chloride (1 equiv). The reaction mixture was allowed to warm to ambient temperature and was stirred at ambient temperature for 16 hours. The reaction was quenched with 3N NaOH, and the aqueous layer was extracted with CH2Cl2. The aqueous layer was acidified with cone. HC1 and filtered through a fritted funnel. The recovered white precipitate was dried under vacuum. (2.1 g, 98%). 1H NMR (400 MHz, CDCI3) d 8.09-7.87 (m, 2H), 7.32-7.26 (m, 2H), 7.07 (s, 1H), 3.12 (s, 3H), 2.61 (s, 3H). LCMS found 214.0 [M+H]+.
95%
With pyridine; at 0 - 20℃; for 2h;
A cooled solution of 4'-aminoacetophenon (10 mmol) in pyridine (10 mL) at 0 C was treated with METHANESULFONYL chloride (15 mmol) and stirred at room temperature for 2 h. The reaction mixture was diluted with HZ0 and extracted with EtOAc several times. The combined organic layers were washed with H20 and brine, dried over MGS04, filtered, and the filtrate was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel using EtOAc: hexanes to afford 4'- (Methylsulfonylamino) acetophenone (13-5, LJO-298). 95% yield, mp = 161 C 1H NMR (CDC13) 8 7.97 (dd, 2 H, J= 2,6. 8 Hz, ), 7.26 (dd, 2 H, J= 2, 6.8 Hz), 6. 87 (bs, 1 H), 3.10 (s, 3 H), 2.59 (s, 3 H)
66%
With pyridine; In tetrahydrofuran; at 20℃; for 12h;
General procedure: To a solution of 4-aminoacetophenone (0.68g, 5mmol) and pyridine (1.6mL, 20mmol) in THF (10mL) was slowly added the substituted sulfonyl chloride (5mmol). The reaction mixture was stirred at room temperature for 12h. Water (50mL) was added and the mixture was extracted with ethyl acetate (10mL×3), the combined organic phase was washed with 1N hydrochloric acid (30mL×2) and water (30mL×2), dried over anhydrous Na2SO4 and concentrated under vacuum to afford the product.
With triethylamine; In dichloromethane; at 0 - 20℃; for 13h;
To a solution of 4-aminoacetophenone (0.5 g, 3.7 mmol) indry CH2Cl2 (10 mL), Et3N (1.18 mL, 8 mmol) was addedfollowed by methanesulphonyl chloride (0.32 mL,4 mmol) at 0 C. After maintaining the temperaturebetween 0 and 5 C for 3-4 h, the reaction mixture wasgradually warmed to room temperature and the contentswere stirred overnight. Once TLC indicated the completionof the reaction, the mixture was diluted with CH2Cl2(20 mL) and washed with water (2 9 15 mL) followed bysaturated sodium chloride solution (15 mL). Drying(Na2SO4) and then distillation of the organic extractsafforded the crude intermediate 3h as a light yellow solid.To the crude 4-methanesulphonamide acetophenone dissolvedin rectified spirit (30 mL), benzaldehyde (1.01 mL,10 mmol) was added followed by an aqueous solution of10 % KOH (10 mL). The mixture was stirred and keptovernight at room temperature. The contents of the reactionmixture were poured into crushed ice and acidified withdilute HCl (0.1-0.2 N). The precipitated chalcone derivativewas filtered off, recrystallised from rectified spirit andfurther purified by column chromatography (20 % EtOAc/cyclohexane) to get yellow crystals.
4'-(methylsulfonylamino)acetophenone oxime[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
91%
With pyridine; hydroxylamine hydrochloride; at 70℃; for 3h;
A mixture of 4'- (Methylsulfonylamino) acetophenone (13-5,5 mmol) and hydroxylamine hydrochloride (0.695 g, 10 mmol) in pyridine (5 mL) was heated at 70 C for 3 h. The reaction mixture was cooled to room temperature, diluted with H20, and extracted with EtOAc several times. The combined organic layers were washed with H20 and brine, dried over MGS04, filtered, and the filtrate was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel using EtOAc: hexanes (1: 1) as eluant to 4'- (Methylsulfonylamino) acetophenone oxime (13-8, LJO-299). 91% yield, white solid, mp = 180 C 'H NMR (CDC13) 6 7.65 (dd, 2 H, J= 2,6. 6 Hz, ), 7.29 (s, 1 H), 7.20 (dd, 2 H, J= 2, 6. 8 Hz), 6.43 (bs, 1 H), 3.03 (s, 3 H), 2.26 (s, 3 H)
With hydroxylamine hydrochloride; sodium acetate; In ethanol; water;
Step 2 Synthesis of 4-methanesulfonylaminoacetophenonoxime (36-2) 4-methanesulfonylaminoacetophenone (36-1) (360.2 mg) was dissolved in ethanol and to the solution was added a solution of hydroxylamine hydrochloride (129.11 mg) and sodium acetate (249.40 mg) in minimal amount of water. To the mixture was added ethanol until the solution became clear and then the solution was refluxed for 20 hours, thereby to be changed from transparent yellow to transparent colorlessness. After confirming the completion of the reaction using TLC, the ethanol was removed therefrom, and the residue was extracted with ethyl acetate, washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentratd under reduced pressure to obain a solid. The solid was recrystallized with ethyl acetate and hexane to yield a pale yellow crystal (289.6 mg, 75.11%) mp: 181.5- 182.1 C.; 1H NMR(400 MHz, CDCl3): delta 7.60(d, 2H, J=7.2 Hz), 7.26(d, 2H, J=7.4 Hz), 2.96(s, 3H), 2.21(s, 3H). IR(KBr pellet, cm-1): 3495.35, 3255.25, 3023.84, 2926.38, 1605.45, 1323.89, 1155.15;
With pyridine; sodium hydrogencarbonate; In dichloromethane;
Step 1 Synthesis of 4-methanesulfonylaminoacetophenone (36-1) 4-aminoacetophenone (300 mg) was dissolved in dichloromethane, and to the solution were added methanesulfonic anhydride (2.44 mimol) and pyridine (53.85 mul) at 0 C., followed by stirring at room temperature for 3 hours. After confirng the completion of the reaction using TLC, the reaction was quenched with saturated sodium bicarbonate solution. The reaction mixture was diluted with dichloromethane, washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain a solid. The solid was recrystallized with ethyl acetate and hexane, to yield a pale yellow crystal (293.2 mg, 61.95%). mp: 155.1-161.2 C.; 1H NMR(400 MHz, CDCl3): delta 7.98(d, 2H, J=8.8 Hz), 7.27(d, 2H, J=8.8 Hz), 3.11(d, 3H, J=1.6 Hz),2.59(d, 3H, J=1.6 Hz) IR(KBr pellet, cm-1): 3290.93, 3003.59, 2928.38, 1667.16, 1600.63, 1469.49, 1330.64, 1279.54, 1146.47
N-(4-acetyl-2-chlorophenyl)methanesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In ethyl acetate-pet; water;
PREPARATION 11 3'-Chloro-4'-((methylsulfonyl)amino)acetophenone, (Halogenation) To 2.13 g (10 mmole) of <strong>[5317-89-5]N-(4-acetylphenyl)methanesulfonamide</strong> in 50 ml of alcohol and 50 ml of water at 30 C. is added 1.43 g (10 mmol) of calcium hypochlorite. The solution is stirred for 24 hrs and an additional 1.43 g of calcium hypochlorite added. The mixture is stirred for 3 days at room temperature. The mixture is acidified with acetic acid to pH 6; concentrated and extracted into water-methylene chloride. The organic layer is dried, evaporated and the residue flash chromatographed on silica gel eluding in succession with 25% and 50% ethyl acetate-pet. ether. The solid product is recrystallized from Et2 O-pet. ether; m.p. 129-131 C. MW 247.71. Anal. [C9 H10 ClNO3 S] Found: C,43.43; H, 3.75; N, 5.55; Cl, 14.47.
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane;
PREPARATION 12 3'-Bromo-4'-((methylsulfonyl)amino)acetophenone, (Halogenation) A mixture of 2.13 g (10 mmol) of <strong>[5317-89-5]N-(4-acetylphenyl)methanesulfonamide</strong>, 1.78 g (10 mmol) of N-bromosuccinimide and 0.28 g of dibenzoyl peroxide in 100 ml of carbon tetrachloride is heated for 16 hrs at 80 C. (oil bath). The resulting product is concentrated and extracted with methylene chloride. The extract is deposited on silica gel and chromatographed with 1% methanol-methylene chloride to give a product which is recrystallized from methylene chloride-pet. ether; m.p. 124-126 C. MW 292.17. Anal. [C9 H10 BrNO3 S] Found: C, 36.58; H, 3.47; N, 4.85; Br, 28.58.
4-[N-benzylmethanesulphonamido]acetophenone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In dichloromethane; butanone;
(A) 4-[N-Benzylmethanesulphonamido]acetophenone STR55 <strong>[5317-89-5]4-(Methanesulphonamido)acetophenone</strong> (50 g), benzyl bromide (40.1 g) and potassium carbonate (32.5 g) in methyl ethyl ketone were stirred at reflux temperature for 4 hours. After cooling the solvent was evaporated and the residue was taken up in methylene chloride and washed twice with water, three times with 2M sodium hydroxide and twice with brine. The organic layer was dried and evaporated to give a solid which was triturated with ether and recrystallized from ethyl acetate to give the title compound, yield 62 g, m.p. 122-123. Analysis %: Found: C, 63.7; H, 5.6; N, 4.7; Calculated for C16 H17 NO3 S: C, 63.3; H, 5.65; N, 4.6.
With hydrogenchloride; paraformaldehyde; In ethanol; acetone;
Compound 3 A mixture of 4'-acetylmethanesulfonanilide (21.5 g., 0.1 mole), 95% paraformaldehyde (10 g., 0.3 mole), pyrrolidine hydrochloride (10.8 g., 0.1 mole) in 150 ml. of ethanol containing 1 drop of concentrated hydrochloric acid is refluxed for a period of 4 hr. at steam bath temperature and then for an additional period of 8 hr. permitting the ethanol to evaporate. The resulting glassy residue is stirred with 300 ml. of hot acetone providing a crystalline material which is collected and crystallized from methanol-isopropyl alcohol to afford analytically pure 4'-[3-(1-PYRROLIDINYL)PROPIONYL]-METHANESULFONANILIDE HYDROCHLORIDE, m.p. 182.0-183.0C. Analysis. Calcd. for C14 H20 N2 O3 S.HCl: C, 50.52; H, 6.36; N, 8.42. Found: C, 50.65; H, 6.48; N, 8.32.
(E)-N-(4-(1-(2-(4-(methylsulfonyl)phenyl)hydrazono)ethyl)phenyl)methanesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
In ethanol; for 12h;Reflux;
General procedure: To a solution of the appropriate acetophenone (0.04 mol) in 20 mLethanol, 4-methanesulfonyl phenyl hydrazine hydrochloride (6a,0.04 mol) was added. The resulting solution was heated under reflux for12 h. The precipitated hydrazones was filtered and washed with sufficientamount of ethanol and recrystallized from ethanol to afford hydrazones8a, 8b and 8f. Physical and spectral data are listed below:
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