Other substitution methods using electrophiles

The alkene bond of 3-sulfolene (and some derivatives) is quite reactive to electrophiles and this allows access to 3-substituted sulfolenes through addition-elimination reactions. 

John Leonard, Andrew B. Hague and John A. Knight 

Hydrobromination of 3-sulfolene is also a useful method for adding functionality to the ring (see Section 6.2). 

Several methods for sulfolene substitution have been devised which utilize bromo groups to introduce other substituents into the sulfolene ring. 

It was found that 4-bromo-2-sulfolenes can also be reacted with electrophilic carbonyl reagents in the presence of Zn-Ag with sonication, providing alcohols 

---

This and other older methods, which have been reviewed previously (21, 22), have been largely superceded in the laboratory by more controlled, selective reactions, starting from suitable thiophene precursors. We shall discuss two major reactions which can be used for the preparation of alkylthiophenes electrophilic substitution of thiophenes and the formation and reactions of lithiated thiophenes. For further details and other aspects of thiophene chemistry the reader is referred to previous reviews (21, 22) and references cited therein. Accounts of yearly developments in thiophene chemistry can also be found in the relevant Royal Society of Chemistry publications. 

This method of preparation of ylides from the corresponding triazolinedi-ones is limited in its synthetic utility. Oxidation of suitable urazolyl compounds seems to be a much more versatile entry to this class of highly reactive dipolar compounds. Starting substituted urazoles are often readily available by simple nucleophilic substitution reactions of urazoles with suitable alkyl halides. As is evident from the preceding sections, many other substituted urazoles can be prepared by the ene-type reaction of TADs, by the reaction of TADs with ketones, or by their electrophilic aromatic substitution reactions. Oxidation of these urazoles, e.g., 501, 428, 504, and 506, can be effected with tert-butyl hypochlorite, or, in some cases, excess PTAD can be used. Various approaches and utilization of this synthetic strategy are best seen in the following examples. 

Besides electrophilic sulfonation, sulfonated phosphines can be produced by nucleophilic substitution reactions using PH3, primary or secondary phosphines, and fluoroarenes in superbasic media. This method has been applied for the synthesis of pura-isomer of TPPTS (p-TPPTS) (Scheme 10) as well as dozens of other interesting ligands including chelating, chiral, and amphiphilic phosphines (a selection is in Scheme 11). ... 

This second example provides a comparison between two different synthetic strategies. One method uses a pathway that maintains the integrity of the core throughout, whereas the other, newer, method builds the core up with the substituents already attached and in place. This second technique is very powerful when complex core structures are required or where lateral substitution in the core is difficult to achieve using conventional electrophilic substitution techniques [39],... 

The most widely used reactions are those of electrophilic substitution, and under controlled conditions a maximum of three substituting groups, e.g. -NO2 (in the 1,3,5 positions) can be introduced by a nitric acid/sul-phuric acid mixture. Hot cone, sulphuric acid gives sulphonalion whilst halogens and a Lewis acid catalyst allow, e.g., chlorination or brom-ination. Other methods are required for introducing fluorine and iodine atoms. Benzene undergoes the Friedel-Crafts reaction. ... 

A is a parameter that can be varied to give the correct amount of ionic character. Another way to view the valence bond picture is that the incorporation of ionic character corrects the overemphasis that the valence bond treatment places on electron correlation. The molecular orbital wavefimction underestimates electron correlation and requires methods such as configuration interaction to correct for it. Although the presence of ionic structures in species such as H2 appears coimterintuitive to many chemists, such species are widely used to explain certain other phenomena such as the ortho/para or meta directing properties of substituted benzene compounds imder electrophilic attack. Moverover, it has been shown that the ionic structures correspond to the deformation of the atomic orbitals when daey are involved in chemical bonds. 

---