Name: 616-83-1|4-Methyl-3-nitrobenzene-1-sulfonyl chloride|98%
Brand: Ambeed
SKU: A241972
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1
[ 88-72-2 ]
[ 616-83-1 ]

Yield	Reaction Conditions	Operation in experiment
83.54%	With chlorosulfonic acid In chloroform at 0 - 20℃;
83.54%	With chlorosulfonic acid In chloroform at 20℃; for 0.75h;
	With chlorosulfonic acid at 25 - 85℃; for 3.41667h;	1.i Placed chlorosulfonic acid (128 mL, 1.91 mmol) in a 500 mL four necked round bottomed flask. Then added 2-nitro toluene (65 mL, 0.547 mmol) drop wise, under stirring in 25 minutes at 25 °C. The reaction mass was heated at 85 °C for 3 hours. Quenched the reaction mass into ice cold water and extracted with ethylacetate (4 x 250 mL), the combined organic layer was washed with brine solution (1 x 100 mL), dried over anhydrous sodium sulfate and solvent was removed under reduced pressure to obtain syrupy product. Yield: 109.5 grams.IR spectra (cm 1): 1381, 1181;1H-NMR ( ppm): 2.76 (3H, s), 7.66 - 7.68 (1H, d, J = 8.2 Hz), 8.14 - 8.17 (1H, dd, J = 8.20, 2.0 Hz), 8.63 (1H, d, J = 1.9 Hz).

	With chlorosulfonic acid at 85℃; for 3h;	1.i Step (i): Preparation of 4-methyl-3-nitro benzenesulfonyl chloridePlaced chlorosulfonic acid (128 mL, 1.91 mmol) in a 500 mL four necked round bottomed flask. Then added 2-nitro toluene (65 mL, 0.547 mmol) drop wise, under stirring in 25 minutes at 25° C. The reaction mass was heated at 85° C. for 3 hours. Quenched the reaction mass into ice cold water and extracted with ethylacetate (4×250 mL), the combined organic layer was washed with brine solution (1×100 mL), dried over anhydrous sodium sulfate and solvent was removed under reduced pressure to obtain syrupy product. Yield: 109.5 grams.IR spectra (cm-1): 1381, 1181;1H-NMR ( ppm): 2.76 (3H, s), 7.66-7.68 (1H, d, J=8.2 Hz), 8.14-8.17 (1H, dd, J=8.20, 2.0 Hz), 8.63 (1H, d, J=1.9 Hz).
	Stage #1: 1-methyl-2-nitrobenzene With chlorosulfonic acid at 110 - 115℃; for 3.5h; Stage #2: With thionyl chloride; N,N-dimethyl-formamide at 60 - 65℃; for 3h;	1.1 (1) Synthesis of 3-nitro-4-methylbenzenesulfonyl chloride Chlorosulfonic acid (559.2 g / 4.8 mol) was added to a 1 L four-necked flask, and the temperature was raised to 110 to 115 ° C by heating,To maintain the temperature, slowly drop o-nitrotoluene (548. 0g / 4.0mol), drop is completed,Continue to heat reaction 3. 5 hours to stop the reaction, the reaction solution to cool to 60 ~ 65 ° C,Add 1mL of DMF, maintain the temperature, slowly dropping thionyl chloride (547. 5g / 4.6mol), drop is completed, continue to heat reaction 3 hours, obtained 3-nitro-4-methyl benzene sulfonyl chloride Of the mixture, directly for the next reaction.
	With chlorosulfonic acid

Reference： [1]Srikanth; Debnath, Bikash; Jha, Tarun [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 6, p. 1841 - 1854]
[2]Srikanth; Kumar; Ghosh, Balaram; Jha, Tarun [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 7, p. 2119 - 2131]
[3]Current Patent Assignee: SUVEN LIFE SCIENCES LIMITED - WO2011/83487, 2011, A1 Location in patent: Page/Page column 27
[4]Current Patent Assignee: SUVEN LIFE SCIENCES LIMITED - US2013/5709, 2013, A1 Location in patent: Page/Page column 10
[5]Current Patent Assignee: HUBEI HUIDA TECHNOLOGY DEV; BEIJING YINGLI JINGHUA TECHNOLOGY DEV - CN103772243, 2016, B Location in patent: Paragraph 0052; 0053; 0054
[6]Current Patent Assignee: Chem.Fabr. v. Heyden - DE89997, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 4, p. 39][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 4, p. 39]

2
[ 616-83-1 ]
bis-(4-methyl-3-nitro-phenyl)-disulfide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen bromide; acetic acid; phenol
	With hydrogen iodide at 25 - 110℃; for 3.5h;	1.ii 4-Methyl-3-nitro benzenesulfonyl chloride (obtained from above step) was placed in a 500 mL four necked round bottomed flask (50 grams, 0.212 mmol). Added hydroiodic acid (89 mL, 0.636 mmol), over a period of 30 minutes, through dropping funnel at 25 °C. The reaction mass was heated at 1 10 °C for 3 hours. Then the mass was cooled to room temperature and quenched into ice cold water. Sodium bi sulfite was added in portions under efficient stirring. The solids, that separated, were filtered on buckner funnel and dissolved in dichloromethane (500 mL). The aqueous layer was removed and the organic layer was washed with brine solution (2 x 50 mL) and dried, over anhydrous sodium sulfate. Solvent was distilled off on rotavapour under vacuum to obtain product. Yield: 22.8 gramsMelting Range: 80.1 - 82.5 °C;IR spectra (cm 1): 1339, 879;'H-NMR ( ppm): 2.57 (3H, s), 7.30 - 7.32 (1H, d, J = 8.0 Hz), 7.59 - 7.61 (1H, dd, J = 8.0, 1.9 Hz), 8.09 (1H, d, J = 1.9 Hz).
	With hydrogen iodide at 110℃; for 3h;	1.ii Step (ii): Preparation of 4,4'-Dimethyl-3,3'-dinitro diphenyl disulfide4-Methyl-3-nitro benzenesulfonyl chloride (obtained from above step) was placed in a 500 mL four necked round bottomed flask (50 grams, 0.212 mmol). Added hydroiodic acid (89 mL, 0.636 mmol), over a period of 30 minutes, through dropping funnel at 25° C. The reaction mass was heated at 110° C. for 3 hours. Then the mass was cooled to room temperature and quenched into ice cold water. Sodium bi sulfite was added in portions under efficient stirring. The solids, that separated, were filtered on buckner funnel and dissolved in dichloromethane (500 mL). The aqueous layer was removed and the organic layer was washed with brine solution (2×50 mL) and dried over anhydrous sodium sulfate. Solvent was distilled off on rotavapour under vacuum to obtain product. Yield: 22.8 gramsMelting Range: 80.1-82.5° C.;IR spectra (cm-1): 1339, 879;1H-NMR ( ppm): 2.57 (3H, s), 7.30-7.32 (1H, d, J=8.0 Hz), 7.59-7.61 (1H, dd, J=8.0, 1.9 Hz), 8.09 (1H, d, J=1.9 Hz).

Reference： [1]Lukaschevitsch [Doklady Akademii Nauk SSSR, 1955, vol. 103, p. 627,629][Chem.Abstr., 1956, vol. 50, # 5556]
[2]Current Patent Assignee: SUVEN LIFE SCIENCES LIMITED - WO2011/83487, 2011, A1 Location in patent: Page/Page column 27
[3]Current Patent Assignee: SUVEN LIFE SCIENCES LIMITED - US2013/5709, 2013, A1 Location in patent: Page/Page column 10

3
[ 98-59-9 ]
[ 616-83-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sulfuric acid; nitric acid for 2h; Ambient temperature;
	With nitric acid
	With sulfuric acid; nitric acid unter Vermeidung von Temperaturerhoehung;

Reference： [1]Cournoyer, Richard; Evans, David H.; Stroud, Stephen; Boggs, Roger [Journal of Organic Chemistry, 1991, vol. 56, # 14, p. 4576 - 4579]
[2]Fox; Turner [Journal of the Chemical Society, 1930, p. 1853,1860]
[3]Reverdin; Crepieux [Bulletin de la Societe Chimique de France, 1901, vol. <3> 25, p. 1041][Chemische Berichte, 1901, vol. 34, p. 2993]

4
[ 616-83-1 ]
[ 6949-23-1 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia

Reference： [1]Semenov, V. P.; Andreeva, T. D.; Ogloblin, K. A. [Journal of Organic Chemistry USSR (English Translation), 1988, vol. 24, p. 195 - 198][Zhurnal Organicheskoi Khimii, 1988, vol. 24, # 1, p. 217 - 220]

5
[ 616-83-1 ]
[ 124-40-3 ]
[ 96-57-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	In dichloromethane; water at 0℃; for 0.5h;
94%	In dichloromethane; water at 0 - 20℃;	5 To a solution of dimethylamine in H2O (40% w/w, 15.0 mL, 120 mmol) at 0 0C was added a solution of 4-methyl-3-nitro-benzenesulfonyl chloride (9.42 g, 40 mmol) in DCM (60 mL) over 30 min. The resulting mixture was stirred at 0 °C for 30 min before being allowed to warm to RT and stirred overnight. The reaction mixture was diluted with H2O (100 mL) and DCM (40 mL), and the layers were separated. The organic layer was washed in succession with water, HCl (aq., 0.1 M) and brine before being dried over Na2SO4 and evaporated to dryness to give the title compound as a pale yellow solid (9.13 g, 94 %). [M + H]+ 244.9
94%	In dichloromethane; water at 0 - 20℃;	8 Reference Example 8; 4-iyV-Trimethyl-3-nitro-benzenesulfonamide; To a solution of dimethylamine in H2O (40% w/w, 15.0 mL, 120 mmol) at 0 0C was added a solution of 4-methyl-3-nitro-benzenesulfonyl chloride (9.42 g, 40 mmol) in DCM (60 mL) over 30 min. The resulting mixture was stirred at 0 0C for 30 min before being allowed to warm to RT and stirred overnight. The reaction mixture was diluted with H2O (100 mL) and DCM (40 mL), and the layers were separated. The organic layer was washed in succession with water, HCl (aq., 0.1 M) and brine before being dried over Na2SO4 and evaporated to dryness to give the title compound as a pale yellow solid (9.13 g, 94 %). [M + H]+ 244.9

94%	In dichloromethane; water at 0 - 20℃;	2 Reference Example 2; 4-NJV-Trimethyl-3-nitro-benzenesulfonamide; To a solution of dimethylamine in H2O (40% w/w, 15.0 mL, 120 mmol) at 0 °C was added a solution of 4-methyl-3-nitro-benzenesulfonyl chloride (9.42 g, 40 mmol) in DCM (60 mL) over 30 min. The resulting mixture was stirred at 0 °C for 30 min before being allowed to warm to RT and stirred overnight. The reaction mixture was diluted with H2O (100 mL) and DCM (40 mL), and the layers were separated. The organic layer was washed in succession with water, HCl (aq., 0.1 M) and brine before being dried over Na2SO4 and evaporated to dryness to give the title compound as a pale yellow solid (9.13 g, 94 %). [M + H]+ 244.9
94%	In dichloromethane; water at 0 - 20℃;	3 Reference Example 3: 4-iVJV-TrimethvI-3-nitro-benzenesuIfonamide; To a solution of dimethylamine in H2O (40% w/w, 15.0 mL, 120 mmol) at 0 0C was added a solution of 4-methyl-3-nitro-benzenesulfonyl chloride (9.42 g, 40 mmol) in DCM (60 mL) over 30 min. The resulting mixture was stirred at 0 °C for 30 min before being allowed to warm to RT and stirred overnight. The reaction mixture was diluted with H2O (100 mL) and DCM (40 mL), and the layers were separated. The organic layer was washed in succession with water, HCl (aq., 0.1 M) and brine before being dried over Na2SO4 and evaporated to dryness to give the title compound as a pale yellow solid (9.13 g, 94 %). [M + H]+ 244.9
94%	In dichloromethane; water at 0 - 20℃;	4 Reference Example 4: 4JVJV-TrimethvI-3-nitro-benzenesuIfonamide; To a solution of dimethylamine in H2O (40% w/w, 15.0 mL, 120 mmol) at 0°C was added a solution of 4-methyl-3-nitro-benzenesulfonyl chloride (9.42 g, 40 mmol) in DCM (60 mL) over 30 min. The resulting mixture was stirred at 0°C for 30 min before being allowed to warm to RT and stirred overnight. The reaction mixture was diluted with H2O (100 mL) and DCM (40 mL), and the layers were separated. The organic layer was washed in succession with water, HCl (aq., 0.1 M) and brine before being dried over Na2SO4 and evaporated to dryness to give the title compound as a pale yellow solid (9.13 g, 94 %). [M + H]+ 244.9
88%	In dichloromethane at 20℃;	General procedure for the formation of nitrotoluene derivatives 7a-c,e,n-p, 10, 13b-c General procedure: A solution of commercially available (6, 12) or previously synthesized benzenesulfonylchloride (9) [S1] in CH2Cl2 (8.0 mL for 5 mmol of benzenesulfonylchloride) was added dropwise to the appropriate amine (3 eq) and the reaction was kept under stirring at RT. Once the disappearance of the precursor was verified by TLC (30 min-16 h), the reaction mixture was acidified with 1N aqueous HCl, extracted several times with CH2Cl2 and the combined organic phase was dried over anhydrous sodium sulphate. Evaporation under vacuum of the organic solvent afforded a crude product which was purified by column chromatography over silica gel, to yield the sulfonamidic derivatives.

Reference： [1]Cournoyer, Richard; Evans, David H.; Stroud, Stephen; Boggs, Roger [Journal of Organic Chemistry, 1991, vol. 56, # 14, p. 4576 - 4579]
[2]Current Patent Assignee: ROCHE HOLDING AG - WO2009/53715, 2009, A1 Location in patent: Page/Page column 51-52
[3]Current Patent Assignee: ROCHE HOLDING AG - WO2007/122410, 2007, A1 Location in patent: Page/Page column 64
[4]Current Patent Assignee: ROCHE HOLDING AG; UNIVERSITY OF LONDON - WO2008/125835, 2008, A1 Location in patent: Referential example 2
[5]Current Patent Assignee: ROCHE HOLDING AG; UNIVERSITY OF LONDON - WO2008/125839, 2008, A2 Location in patent: Page/Page column 37
[6]Current Patent Assignee: ROCHE HOLDING AG; UNIVERSITY OF LONDON - WO2008/125833, 2008, A1 Location in patent: Page/Page column 37
[7]Granchi, Carlotta; Roy, Sarabindu; Mottinelli, Marco; Nardini, Elisa; Campinoti, Fabio; Tuccinardi, Tiziano; Lanza, Mario; Betti, Laura; Giannaccini, Gino; Lucacchini, Antonio; Martinelli, Adriano; MacChia, Marco; Minutolo, Filippo [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7331 - 7336]

6
[ 616-83-1 ]
[ 74-89-5 ]
[ 108227-52-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	In dichloromethane; water at 0℃; for 0.5h;
	In tetrahydrofuran for 3h; Reflux;	9.a a) A/,4-dimethyl-3-nitrobenzenesulfonamideA mixture of 4-methyl-3-nitrobenzenesulfonyl chloride (0.350 g, 1 .485 mmol) and DMAP (0.036 g, 0.297 mmol) in CH3NH2 (2.971 mL, 5.94 mmol of a 2 M solution in THF) was heated at reflux for 1 h. Additional CH3NH2 (2.97 mL, 5.94 mmol of a 2 M solution in THF) was added and the resulting mixture stirred at reflux for an additional 2 h. The reaction was then cooled, filtered, and the filtrate concentrated to afford the title compound.

Reference： [1]Cournoyer, Richard; Evans, David H.; Stroud, Stephen; Boggs, Roger [Journal of Organic Chemistry, 1991, vol. 56, # 14, p. 4576 - 4579]
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2011/149827, 2011, A1 Location in patent: Page/Page column 62

7
[ 31252-42-3 ]
[ 616-83-1 ]
[ 228552-26-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In tetrahydrofuran at 0 - 20℃; for 24h;

Reference： [1]Dominguez, Celia; Duffy, Daniel E.; Han, Qi; Alexander, Richard S.; Galemmo Jr., Robert A.; Park, Jeongsook M.; Wong, Pancras C.; Amparo, Eugene C.; Knabb, Robert M.; Luettgen, Joseph; Wexler, Ruth R. [Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 7, p. 925 - 930]

8
[ 616-83-1 ]
2-dimethylamino-N-[2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-ethyl]-acetamide [ No CAS ]
2-dimethylamino-N-{2-[2-(4-methyl-3-nitro-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinolin-1-yl]-ethyl}-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With polystyrene-bound piperidine In dichloromethane at 20℃; for 96h;