Halogenation heterocycles

Many heterocyclic halogen compounds are capable of quatemizing nitrogen bases and, indeed, of self-condensation, which can occur with great ease (for example, on warming a solution of l-chloro-4-methyl-... 

Cathodic Reduction of Aromatic and Heterocyclic Halogen Compounds... 

Dinonyl phthalate 20 150 I Tol 83 183 147 231 159 For aromatics, heterocycles, halogen compounds... 

Counterpoised to these experimental difficulties are certain distinct advantages to studies of heterocyclic halogenation. In the first place, the halogen family comprises a rationally related series of electrophilic... 

In this survey the emphasis will be placed upon the newer findings in the synthetic and mechanistic aspects of heterocyclic halogenation. As to mechanisms, it appears both necessary and desirable to outline possible views among which present knowledge cannot decide. Hopefully the enthusiasm and curiosity of chemists will be awakened when they appreciate the many unresolved problems in heterocyclic halogenation. 

The structure of ra-complexes has been examined by the X-ray crystallographic studies of solid samples and by the spectral measurement of heterocycle-halogen equilibria in solution. By the former approach the structure of the solid 1 2 pyridine-molecular iodine complex has been shown to consist principally of two pyridine molecules collinearly bonded to an iodine atom and of linear triiodide units. Moreover, in the 1 1 complex of dioxane and bromine, the heterocyclic oxygen-bromine-bromine linkages are also collinear.4 In the latter type of study, interest in the well-known phenomenon of brown iodine solutions has occasioned the measurement of the stability constants for many complexes of halogen and heterocycles.25, 29 Information concerning their structure in solution comes from a consideration of the relative size of such constants as a function of heterocycle structure. Thus, the fact that bromine complexes of both 8-bromo- and 8-methylquinolines possess stability constants (K = 1.1 and 4.8 liters/mole) much smaller than that of quinoline itself... 

In the widest sense, heterocyclic halogenation by substitution embraces the introduction of halogen in place of such groups as hydrogen, metal, carboxylate, amino, and hydroxyl (cf. Section... 

Heterocycle Halogenating agent Position of attack" Reference... 

Precise mechanistic descriptions of heterocyclic halogenation are not possible with the existing experimental information. Still it appears desirable to consider what mechanistic models may be involved in such substitution processes, in an attempt both to correlate what is known and to sharpen the focus of future research. A posteriori, the most appealing reaction models are those viewing... 

In assessing the applicability of the foregoing model to a given heterocyclic halogenation, approaches such as the detection and... 

At present, the most extensive data on heterocyclic halogenation concern the sites of substitution under different experimental conditions. In order to correlate the observed orientation with the previous transition state model, some measure is needed of how readily the various unsaturated carbon sites can provide electronic bonding to the attacking species, the electrophile, X+ (solvated) or... 

As with most fields of chemical research, the synthetic aspects of heterocyclic halogenation have been mastered far better than have the underlying reaction mechanisms. The latter facet is intriguing not only in attaining a more intelligent control of preparative halogenation, but also in mapping the electronic response of extensively... 

The electrode reactions of heterocyclic halogen compounds exhibit generally no special features, but some may be of preparative value. Anodic halogenation may be advantageous in fluorination and iodination reactions and in halogenations in which a low, easily measured concentration of halogen is desirable. 

Heterocyclic halogen-containing groups other than dichlorotriazinyl and chlorotriazinyl have been used in the preparation of reactive dyes. The Reactone and Drimarine colours are substitution products of tetrachloro-pyrimidine, (9), and therefore contain a trichloropyrimidyl group in the molecule, (10). An example of such a dyestuff is Reactone Red 2B, (11). 

Nucleophilic displacement of halogen with ammonia and amines can be accelerated by carrying out the displacements in acid solution, when the protonated heterocycle is more reactive than the neutral heterocycle. Halogen can also be easily removed hydrogenolytically, for example treatment of 2,4-dichloropyrimidine, readily available from uracil, with hydrogen, in the presence of palladium, or with hydrogen iodide, gives pyrimidine itself. ... 

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