Five-membered heterocycles halogenation

Finally, M. R. Grimmett from the University of Otago in New Zealand deals comprehensively with the halogenation of five-membered heterocycles in the first part of a survey that will ultimately cover the halogenation of all heterocycles. 

With five-membered heterocycles principal halogenation takes place alpha to the heteroatom (thiophene at C-238 indole is chlorinated at C-2,53 but iodinated at C-354). 

Similar elimination reactions are employed in the synthesis of the benzologs of five-membered heterocyclic compounds. For example, /3-phenylethyl alcohols having hydroxyl, sulfhydryl, and amino groups in the ortbo position ate cyclized to the dihydro derivatives of benzofuran, benzothiophene, and benzopyrrole, respectively. Likewise, dehydro-halogenation of /3-(o-hydroxyphenyl)-ethyl bromide gives dihydtobenzo-furan in 72% yield. ... 

Like other aromatic compounds, these five-membered heterocycles undergJ nitration, halogenation, sulfonation, and Friedel-Crafts acylation. They are mucji more reactive than benzene, and resemble the most reactive benzene derivatives (amines and phenols) in undergoing such reactions as the Reimer-Tiemann reaction, nitrosation, and coupling with diazonium salts. 

Lithiobenzothiophenes can be generated, and reacted with electrophiles, if the temperature is kept low. Direct deprotonation of benzothiophenes follows the usual pattern for five-membered heterocycles and takes place adjacent to the hetero atom, and in concord with this pattern, metal-halogen exchange processes favour a 2- over a 3-halogen. 2-Trialkylstannylbenzofurans are useful for palladium-catalysed coupling with aromatic halides. ... 

In order to introduce substituents into the 3-position in five-membered heterocyclic rings (such as thiophene) the highly reactive positions (2, 5) must first be blocked. Halogens have proved particularly useful in this capacity e.g. Fig. 1.30. 

Wang et al. reported that FeCls- and FeBrs-promoted cyclization/halogenation of alkynyl diethyl acetals formed ( )-2-(l-halobenzylidene or alkylidene)-substi-tuted five-membered carbo- and heterocycles. It was found that the 1 1 molar ratio... 

---