Halogenation heterocyclic compounds

Piperazinothiazoies (2) were obtained by such a replacement reaction, Cu powder being used as catalyst (25. 26). 2-Piperidinothiazoles are obtained in a similar way (Scheme 2) (27). This catalytic reaction has been postulated in the case of benzene derivatives as a nucleophilic substitution on the copper-complexed halide in which the halogen possesses a positive character by coordination (29). For heterocyclic compounds the coordination probably occurs on the ring nitrogen. 

Free-radical substitutions of heterocyclic compounds have been carried out with alkyl, aryl, and hydroxyl radicals in solution and with halogen atoms in the gas phase. Of these, arylations have been the most extensively investigated. 

Gas-phase halogenation of benzenoid and heterocyclic compounds has been extensively studied by Wibaut and his co-workers, and a review of this work is available. ... 

The final chapter is by M. R. Grimmett of Otago, New Zealand, and is the third and final part of his survey of the halogenation of heterocyclic compounds. It deals with the halogenation of condensed heterocycles. The first two parts of this series appeared in Volumes 57 and 58 of Advances. 

Electrophilic radicals, such as halogen atoms, hydroxy, alkoxy, and amino radicals, do not seem to have great value in reactions with heterocyclic compounds. 

In spite of the fact that cesium fluoride is very expensive and needs care in handling (very hygroscopic ), it is the reagent of choice for several reactions where halogens and fluorosulfonate groups have to be replaced by fluorine in aromatic and heterocyclic compounds. Cesium fluoride is more reactive than potassium fluoride and also possesses greater solubility. Often a phase-transfer catalyst is added to aid and enhance the reaction rate and yield of the products. 

Heterocyclic compounds range from those, such as furan which is readily halogenated and tends to give polyhalogenated products, to pyridine which forms a complex with aluminum chloride that can only be brominated to 50% reaction (23). 

Halogenation of Aromatic and Heterocyclic Compounds by Means of N-Halogenated Amides N. P. Buu-Hoi, Rec. Chem. Prog., 1952,13, 30-36. 

Biagi et ai. [28] studied the relationship between Kow and reversed-phase TLC retention factor for 28 phenols substituted with alkyl, halogen, methoxy, and nitro groups. Budvari-Barany et al. [29] compare the HPLC and TLC retention method to estimate Kovl for a class of heterocyclic compounds (imidazoquinoline derivatives). Takacs-Novak et al. [30] has demonstrated the similarity between the pH-dependent Kow and the pH-related retention (C i8 /methanol-water) pattern of eight amphoteric compounds in the pH range 4 to 9. 

---