Toward electrophilic reagents sulfonation

Sulfonic, carboxylic, etc., groups present in the substrate may easily undergo substitution (Fig. 8) during Maimich synthesis, due to their reactivity toward electrophilic reagents ... 

When unsubstituted, C-5 reacts with electrophilic reagents. Thus phosphorus pentachloride chlorinates the ring (36, 235). A hydroxy group in the 2-position activates the ring towards this reaction. 4-Methylthiazole does not react with bromine in chloroform (201, 236), whereas under the same conditions the 2-hydroxy analog reacts (55. 237-239. 557). Activation of C-5 works also for sulfonation (201. 236), nitration (201. 236. 237), Friede 1-Crafts reactions (201, 236, 237, 240-242), and acylation (243). However, iodination fails (201. 236). and the Gatterman or Reimer-Tieman reactions yield only small amounts of 4-methyl-5-carboxy-A-4-thiazoline-2-one. Recent kinetic investigations show that 2-thiazolones are nitrated via a free base mechanism. A 2-oxo substituent increases the rate of nitration at the 5-position by a factor of 9 log... 

Pyridine lies near one extreme in being far less reactive than benzene toward substitution by electrophilic reagents. In this respect it resembles strongly deactivated aromatic compounds such as nitrobenzene. It is incapable of being acylated or alkylated under Friedel-Crafts conditions, but can be sulfonated at high temperature. Electrophilic substitution in pyridine, when it does occur, takes place at C-3. 

Chemoselective reaction of epoxy sulfonates represents a more significant challenge, since the two electrophilic moieties are reported to be of nearly equivalent reactivity toward organocuprate reagents. 

A -Phenyl-A -(4-pyridyl)urea reacted normally with excess chlorosulfonic acid (six equivalents) at 70 °C (3 hours) to give the 4 -sulfonyl chloride. In this substrate, sulfonation in the phenyl ring is to be expected since the pyridyl ring is deactivated towards electrophilic substitution by the electron deficient nitrogen atom. However, the 2-pyridyl analogue 391 behaved differently and reacted with an excess of the reagent under similar conditions to give a low yield (20%) of the 2, 4 -disulfonyl chloride 392 (Scheme 13). ... 

The early work on the sulfonation of aliphatic compounds is described in Suter s book there are also several general references " which include the use of chlorosulfonic acid in the sulfonation of aliphatic compounds. Aliphatic compounds are generally less reactive towards sulfonating reagents than aromatic species, because they are less nucleophilic in character and so are less susceptible to attack by an electrophilic reagent like chlorosulfonic acid. 

Perfluoroalkyl(phenyl)iodonium sulfonates 42 (also known as FITS reagents), as well as lFf,lff-perfluoroalkyl(aryl)iodonium triflates 44, have found practical application as electrophilic fluoro alkylating reagents toward a... 

BICYCLOPROPYLIDENE possesses unique reactivity toward a wide range of electrophiles and nucleophilic carbenes. (E)-1-DIMETHYLAMINO-3-tert-BUTYLDIMETHYL-SILOXY-1,3-BUTADIENE is a highly reactive diene for Diels-Alder reactions, as described in an accompanying procedure for the synthesis of 4-HYDROXYMETHYL-2-CYCLOHEXEN-1-ONE via the Diels-Alder reaction with methyl acrylate. Finally, this section concludes with the preparation of DIETHYL [(PHENYLSULFONYL)METHYL]PHOSPHONATE, a reagent that is very useful for synthesis of a. -unsaturated phenyl sulfones. 

Sulfonates. The sulfonates derived from alcohols and the title reagent are good electrophiles toward azide and cyanide ions. 

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