Pyridines halogenation

Attempts to synthesize transition metal alkyl compounds have been continuous since 1952 when Herman and Nelson (1) reported the preparation of the compound C H6>Ti(OPri)3 in which the phenyl group was sigma bonded to the metal. This led to the synthesis by Piper and Wilkinson (2) of (jr-Cpd)2 Ti (CH3)2 in 1956 and a large number of compounds of titanium with a wide variety of ligands such as ir-Cpd, CO, pyridine, halogen, etc., all of which were inactive for polymerization. An important development was the synthesis of methyl titanium halides by Beerman and Bestian (3) and Ti(CH3)4 by Berthold and Groh (4). These compounds show weak activity for ethylene polymerization but are unstable at temperatures above — 70°C. At these temperatures polymerizations are difficult and irreproduceable and consequently the polymerization behavior of these compounds has been studied very little. In 1963 Wilke (5) described a new class of transition metal alkyl compounds—x-allyl complexes,... 

Halogenation of conjugated dienes proceeds chiefly by 1,4-addition with molecular halogens (equation 3). 1,2-Addition is favored in the presence of pyridine-halogen complexes and amine tribromide salts (equation 4)9. The stereochemistry of 1,4-bromine addition with 2,4-hexadienes and cyclopentadiene is primarily anti in the presence of amine, but syn with molecular halogen in the absence of amine. 

Halogenation of pyridines is easier than nitration or sulfonation because it can be carried out in non-acidic media and the pyridine-halogen adducts are appreciably dissociated. Dihalogenation can occur since one halogen atom causes little additional deactivation of the ring. The mercuration of pyridines (Section 3.2.1.4.9) probably involves coordination of the pyridine nitrogen to the mercury atom, and such coordination causes less ring deactivation than protonation. 

Pyridine-halogen complexes (73) dissociate on heating halogen is lost so readily that these compounds act as mild halogenating agents toward phenol or aniline, for example (see Section 3.2.1.3.8). 

The general trend is to increase the selectivity of the addition. Selectivity is often increased by substituting pyridine-halogen charge transfer complexes or tribromides of organic bases for the free halogens. Instead of pyridine an insoluble polymer can be applied. Although the rate of reaction is lower compared to the almost instantaneous reaction of free bromine, this technique facilitates isolation and purification of the product. ... 

Consequently, pyridine has a reduced susceptibility to electrophilic substitution compared to benzene, while being more susceptible to nucleophilic attack. One unique aspect of pyridine is the protonation, alkylation, and acylation of its nitrogen atom. The resultant salts are still aromatic, however, and they are much more polarized. Details for reactivity of pyridine derivatives, in particular, reactions on the pyridine nitrogen and the Zincke reaction, as well as C-metallated pyridines, halogen pyridines, and their uses in the transition metal-catalyzed C-C and C-N cross-coupling reactions in drug synthesis, will be discussed in Section 10.2. 

The pyridine-halogen complexes form salts with acids, the halogen being... 

N] halogen bonds by investigation of flexible and structurally restrained [bis (pyridine)halogen] complexes (Fig. 10) [80, 81]. 

Haque I, Wood JL (1967) The infra-red spectra of pyridine-halogen complexes. Spectrochim Acta A 23 959-967... 

Sabin JR (1972) Some calculations on lighter bis(pyridine)halogen(I) cations. J Mol Struct... 

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