Sulfonyl halides rings

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

Amino-l,2,4-thiadiazoles (16) readily yield monoacylated derivatives of type (129) under the usual conditions whereas both monoacyl and diacyl derivatives (130 and 131, respectively) are easily obtained from the 3-amino isomers (65AHC(5)119, 70CB1805). In a similar manner the 3-amino-l,2,4 thiadiazoles produce mono- and di-sulfenamide derivatives when treated with sulfenyl halides. In general, the reactions of 3-amino- and 5-amino-1,2,4-thiadiazoles with sulfonyl halides under basic conditions produce only low yields of the desired derivatives. Sulfonamides of type (132) are best prepared by ring synthesis methods as illustrated in Scheme 55 (75LA1961). 

Irreversible reactions of carbohydrates include the formation of glycosides and 1-deoxy-l-thioglycosides from acylglycosyl halides and thio-acetals, " respectively, esterifications by acyl and sulfonyl halides or anhydrides in pyridine, displacements of sulfonyloxy groups by various reagents, and most examples of formation and scission of anhydro rings, It is more difficult to define the influence of stereo effects on the course of these reactions and some of the results obtained await explanation. 

General Discussion. Various kinetic and reactivity studies have been performed using TsBr alone or in comparison with other arene sulfonyl halides. Most of the literature describes the use of this reagent to initiate free radical ring formation, predominantly for five-membered ring systems. There are, however, reports of its use in vinyl sulfone and thiolsulfonate formation and in halogenation reactions. 

Friedel-Crafts (and Other Aromatic Functionalization) Reactions. When treated with AgOTf, alkyl, acyl (eq 4), and sulfonyl halides are converted to extremely electrophilic triflate species that react rapidly with even deactivated aromatic rings in the absence of catalysis. Benzylic chloroformates participate similarly (eq 5). Aromatic rings are also efficiently vinylated and iodinated via AgOTf-promoted processes. 

Aromatic sulfonyl chlorides can be prepared directly, by treatment of aromatic rings with chlorosulfuric acid. ° Since sulfonic acids can also be prepared by the same reagent (11-7), it is likely that they are intermediates, being converted to the halides by excess chlorosulfuric acid. The reaction has also been effected with bromo-and fluorosulfuric acids. 

N- Hydroxyindoles can be alkylated by primary halides to give 1-alkoxyindoles which, while not extensively studied, appear to show the chemical reactions characteristic of the indole ring (78JCS(Pl)1117). 1-Acyloxyindoles can be prepared from N-hydroxyindoles and acid anhydrides or acyl halides and are fairly stable thermally. Attachment of the more electronegative sulfonyl group, however, leads to facile rupture of the N—O bond and formation of 3-sulfonyloxyindoles (equation 194) (81CPB1920). 

Polysulfonylation. The polysulfonylation route to aromatic sulfone polymers was developed independently by Minnesota Mining and Manufacturing (3M) and by Imperial Chemical Industries (ICI) at about the same time (81). In the polymerization step, sulfone links are formed by reaction of an aromatic sulfonyl chloride with a second aromatic ring. The reaction is similar to the Friedel-Crafts acylation reaction. The key to development of sulfonylation as a polymerization process was the discovery that, unlike the acylation reaction which requires equimolar amounts of aluminum chloride or other strong Lewis acids, sulfonylation can be accomplished with only catalytic amounts of certain halides, eg, FeQ3, SbQ, and InCl3. The reaction is a typical electrophilic substitution by an arylsulfonium cation (eq. 13). 

Mesylates are used for Ni-catalysed reactions. Arenediazodium salts 2 are very reactive pseudohalides undergoing facile oxidative addition to Pd(0). They are more easily available than aryl iodides or triflates. Also, acyl (aroyl) halides 4 and aroyl anhydrides 5 behave as pseudohalides after decarbonylation under certain conditions. Sulfonyl chlorides 6 react with evolution of SO2. Allylic halides are reactive, but their reactions via 7t-allyl complexes are treated in Chapter 4. Based on the reactions of those pseudohalides, several benzene derivatives such as aniline, phenol, benzoic acid and benzenesulfonic acid can be used for the reaction, in addition to phenyl halides. In Scheme 3.1, reactions of benzene as a parent ring compound are summarized. Needless to say, the reactions can be extended to various aromatic compounds including heteroaromatic compounds whenever their halides and pseudohalides are available. 

Displacement of halides by secondary amines and of sulfonyl groups by alkoxides can also take place. Furoxancarboxylic acids are attacked by base to give acyclic products, but their derivatives can undergo nucleophilic acyl substitutions. Likewise nucleophilic addition reactions can be accomplished for ketofuroxans, although ring cleavage is also commonplace. The generation of new heterocyclic systems by reaction with nucleophiles is dealt with in Section 4.22.3.2.5. 

Sulfuryl chloride (40) will chlorosulfonate organic molecules in the presence of a Lewis acid, but often ring chlorination also occurs leading to a mixture of products however, improved yields of the sulfonyl chloride (32) often result from the use of the Grignard reagent derived from an alkyl or benzyl halide (Scheme 33). 

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