4- Methyl-3-nitrobenzenesulfonyl chloride

Sulfamethizole Sulfamethizole, AfL(5 niethyl-l,3,4-thiadiazole-2-yl)sulfanilamide (33.1.15), is synthesized in two ways. According to the first, 5-amino-2-methyl-l,3,4-thiadiazole is reacted with 4-nitrobenzenesulfonyl chloride to make a nitro derivative (33.1.14), which is then reduced using iron filings in acetic acid to give the desired sulfamethizole. 

The reaction of methyl ester of D-alanine 185 with 4-methoxy-2-nitrobenzenesulfonyl chloride 186 in presence of ethyl diisopropylamine gave the sulfonamide 187, which was alkylated with allyl bromide 188 to afford 189 (Scheme 41). Ozonolysis of 189 resulted in the formation of aldehyde 190, and the subsequent reductive cyclization with zinc and AcOH led to the benzothiadiazepine 120 through intramolecular reductive alkylation. Using similar reaction sequence, the 1,2,5-thiadiazepines 191 and 192 were also synthesized <2003JME1811>. 

The condensation of 2-nitrobenzenesulfonyl chlorides with 3-amino-2-chloropyridine in the presence of pyridine at 60 °C gave the corresponding sulfonamides, which were reacted with sodium hydride and iodomethane to give the N-methylated products. Catalytic hydrogenation of the N-methylated compounds followed by acetylation, treatment with sodium hydride in DMF, and reaction with arylalkyl chlorides or methanesulfonates resulted in the formation of novel benzo[/]pyrido[]3,2-r-][l,2,5]thiadiazepines <2005JME7363>. 

This starting material can be prepared as follows. 123 parts of finely powdered 6-amino-2,4-dimethylpyrimidine are suspended in 250 parts of dry pyridine and 222 parts of p-nitrobenzenesulfonyl chloride added at 50°C to 55°C. The whole is then warmed for 2 hours to 55°C. Water is added to the crystalline aggregate obtained, the precipitated bis-N-(p-nitrobenzenesulfonyl)-6-amino-2,4-dimethylpyrimidine filtered off by suction and washed with water. It is purified by recrystallizing from methyl ethyl ketone. On slowly heating it decomposes on rapidly heating it melts at about 210°C to 215°C with decomposition. 

Methyl-2-nitrobenzenesulfonyl chloride 621 Bis-(2-nitrotolyl) disulfide (2 g) is dissolved in glacial acetic acid (10 ml), water (2 ml) is added, and the solution is saturated with chlorine whilst being allowed to become warm. On cooling, part of the sulfonyl chloride separates as colorless crystals and the remainder is obtained by evaporation for purification it is recrystallized from benzene-light petroleum, then having m.p. 98-99°. 

DEHYDRATION Diethoxyaluminum chloride. Lithium n-propylmercaptide. N-Methyl-N,N -di-r-butylcarbodiimidium tetrafluoroborate. o-Nitrobenzenesulfonyl chloride. Potassium acetate. Thiobenzoyl chloride. Triphenylphosphine ditriflate. Triphenyl-phosphine methiodide. 

Preparation of Af-Cyano-4-Methyl-A -Phenyl-Benzene-sulfonamide (1). Dehydrative tosylation of iV-phenylurea 2 with p-toluenesulfonyl chloride in pyridine at room temperature gave iV-cyano-4-methyl-iY-phenyl-benzenesulfonamide in 76% yield (eq 1). Notably, title compound 1 is synthesized in a user-friendly and environmentally benign fashion, eliminating the use of toxic cyanation reagents such as BrCN and HCN. Alternative methods of preparation involve the direct tosylation of phenyl cyanamide in pyridine. Structural analogs, such as ben-zenesulfonyl IV-phenyl cyanamide 3 and p-nitrobenzenesulfonyl //-phenyl cyanamide 4, are accessible in a similar manner. ... 

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