Heterocycles halogen substitution

The thermally unstable acethylenic thiols 142, which are produced from the corresponding halogen substituted acetylene derivatives 141, have been reported to undergo, in the presence of hydroquinone and nitrogen at — 15°C, heterocyclization to the derivatives 143, 144, and 145 (Eq. 22). ... 

In the context of mechanistic studies, the electrochemical behavior and reactions with nucleophiles of 4-chloro-2,6-diphenylpyrylium and 4-chloro(bromo)flavylium have been studied <1999CHE653>. The proposed mechanism for nucleophilic substitution in halogen-substituted pyrylium and flavylium salts passes through formation of a charge-transfer complex that is converted into an ion-radical pair by simple electron transfer. Heterocyclic cleavage of the C-halogen bond occurs at the stage of the radical or the adduct from the reaction of the pyrylium salt and the nucleophile. In this study, an amine nucleophile was used however, the data are likely relevant for other types of nucleophiles as well (Scheme 5). 

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... 

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... 

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... 

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). 

Halogen substitution produces compounds with decreased activity except when inserted into positions 4 or 9 (e g., fluoxymesterone). Replacement of a carbon atom in position 2 by oxygen has produced the only clinically successful heterocyclic steroid among a number of azasteroids and oxasteroids. Some of the 2-oxasteroids are potent anabolic agents. 

Halogen-substituted aryl and heterocyclic compounds can also be hydrodehalogenated as easily. With NaOAc as the base, iodopyrrole was deiodinated in quantitative yield (Scheme 69). ... 

Other reactive bases can be used in this reaction. Pyridine reacts with phenyllithium at 100°C, for example, to give 2-phenylpyridine. This reaction is limited in scope because powerful nucleophiles are required and the reaction conditions can be harsh. Nonetheless, several interesting transformations are observed. Five-membered ring heterocycles are less prone to nucleophilic aromatic substitution, in part because the reparation of the requisite halogen-substituted derivatives can be difficult. 

Diamines are also obtained from allyl chlorides by initial halogen substitution to give the aUylamine and subsequent hydroaminomethylation [99]. With primary amines or diamines this method can also be nsed in the synthesis of heterocyclic systems. 

---