P-Methoxybenzenesulfonyl chloride

A solution of 40 g. (0.37 mole) of anisole in 150 ml. of chloroform is cooled in an ice-salt bath to —8°, and 86.2 g. (0.74 mole) of chloro-sulfonic acid is added with stirring as rapidly as possible (about 20 minutes) while the temperature of the reaction mixture is maintained at 0°. Stirring is continued for 30 minutes while the temperature increases to room temperature. The mixture is poured into crushed ice and extracted with chloroform. The chloroform solution is washed with three small portions of ice water and is dried first over sodium sulfate and then over Drierite, and the solvent is removed under reduced pressure. Distillation of the residue gives a 66% yield of the sulfonyl chloride boiling at 103-105°/0.25 mm. (bath temperature 120-135°). The product melts at 41-42°. 

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A somewhat different scheme is used to gain entry to the alternate symmetrical 1,3,4-thiadiazole ring system. Reaction of thiosemicarbazide with isovaleric acid affords the ring system (217) in one step. The reaction may be rationalized by positing acylation to intermediate 216 as the first step. Sulfonylation of the amino group of 217 with p-methoxybenzenesulfonyl chloride affords the oral... 

Anisole (methyl phenyl ether) is extremely reactive towards sulfonation due to the presence of the strongly electron-donating (-fM) methoxy group. It therefore reacts with chlorosulfonic acid (two equivalents) at 0 °C to give mainly p-methoxybenzenesulfonyl chloride. With chlorobenzene, the chlorine atom exerts a strong electron-withdrawing (-1 effect) so sulfonation will be rather less easy than for benzene. Treatment of chlorobenzene with chlorosulfonic acid (four equivalents) at 25 C (3 hours) afforded p-chlorobenzenesulfonyl chloride (84%) and di(/7-chlorophenyl sulfone) (6%)." Chlorobenzene with chlorosulfonic acid (six equivalents) at 150-160 °C (8 hours) gave the 2,4-disulfonyl chloride. 

Anisole (methyl phenyl ether or methoxybenzene (187 Ar = Ph, R = Me)) reacts with chlorosulfonic acid (two equivalents) in chloroform at 0 °C to give 4-methoxybenzenesulfonyl chloride the latter was also obtained by treatment of 187 with a mixture of chlorosulfonic acid and sulfuric acid at 10 The chlorosulfonation of o- 189 and p- 190 substituted anisoles by chlorosulfonic acid was also achieved in high yields. The o-isomers 189 generally only required mild conditions e.g. a few minutes at 0 C) the ease of chlorosulfonation is probably due to the lack of steric hindrance in the reactive 4-position. 

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