Electrophilic halogenating agents

Heterocycles of this type are 7r-excessive molecules that usually react very vigorously with electrophilic halogenating agents. Substitution can occur in both a- and j8-positions, with the former the preferred sites, and addition is also frequently observed. The high degree of reactivity makes it difficult to prepare monohalogenated derivatives. 

Fluorine has been used for the generation of extremely strong electrophilic halogenating agents in electrophilic iodination and bromination of deactivated aromatic substrates in highly acidic reacton media. Polyhalogenation of more activated aromatic substrates is also possible (Fig. 90) [231-233]. 

In the presence of SbFs, inorganic halides such as NaCl and NaBr can serve as electrophilic halogenating agents [21b,28]. The halogenation of alkanes with dichloro- or dibromomethane has been achieved in the presence of SbFs (Eq. 13) [29], In this reaction, halonium ions are initially formed these in turn abstract hydride from hydrocarbons. Quenching of the resulting carbocations with halides leads to the desired haloalkanes. 

The general concept is that sulfur is introduced into the organic substrate as a direct synthetic precursor of fluorine. Tlte sulfur compound is then treated with a thiophilic, soft electrophilic oxidant, for example electrophilic halogenation agents (NBS, NIS, DBH, Br2, SO2CI2 [148], Fj [149], IF5 [150], BrFj [151], 4-MePhIF2 [152], or nitrosyl cations (NO BF., ) [146] in the presence of a fluoride source (50% or 70% HF-pyridine [143], HF-melamine [144], NEt3 3HF) [147]. 

Friedel-Crafts reaction Activation by Sm(OTf)3 an electrophilic halogenating agent attacks alkenes and thereby gravitating the alkylation of arenes. 

There exist three fundamental ways to prepare OSCN (1) hydrolysis of thiocyanogen, (SCN)2 in aqueous base (2) enz5une-catalyzed oxidation of SCN by H2O2 and (3) oxidation of SCN by electrophilic halogenating agents. The advantages and disadvantages of each of these methods will be discussed next. 

Nucleophiles RNH2, RR NH, EtOH, KOH, RSH, and ArMgBr have been reported to react with l,3-diphenylbenzo[e][l,2,4]triazin-7(l//)-one regioselectively at C(6), whereas the electrophilic halogenating agents attack exclusively the C(8) position. ... 

As with addition of other electrophiles, halogenation of conjugated dienes can give 1,2- or 1,4-addition products. When molecular bromine is used as the brominating agent in chlorinated hydrocarbon solvent, the 1,4-addition product dominates by 7 1 in the case of butadiene. ... 

It becomes clear that in all these compounds it is the conjugate base that takes part in the substitution proper. For mono- and particularly 1,3-dicarbonyl compounds this result actually removes the problem of whether it is the keto or the enol form which enters into an electrophilic substitution by diazonium ions, halogenating agents, and many other reagents. The keto and the enol form are distinct species, but they have one (common) conjugate base This was made clear quite early, but even today there are many chemists who seem not to be aware of it. 

Acetoxylation is found to accompany nitration of fairly reactive aromatics by nitric acid in acetic anhydride and gives rise to zeroth-order kinetics76. The electrophile is believed to be protonated acetyl nitrate the formation of which is rate-determining, hence the kinetic order (see p. 37). Acetoxylation can also accompany halogenation by positive halogenating agents in acetic acid solvent, especially in the presence of sodium acetate137, but no kinetic studies have been carried out. 

The usual oxidizing agents transfer oxygen (or halogens and related species with subsequent hydrolysis) stepwise to the sulfur of thioethers Rates of step A compared with those of step B are faster with electrophilic oxidation agents (peroxy acids) inversely, rates of step B compared with those of step A are faster with nucleophilic oxidation agents (peroxy anions)339-341. 

The C-3 atom of 4-oxo-4/f-pyrido[l,2-a]pyrimidines readily takes part in electrophilic substitutions. 4-Oxo-4//-pyrido[ 1,2-a]pyrimidines unsubstituted at position 3 may be transformed by nitrating agents to the 3-nitro derivatives37 42,52 96,1 16,293 and by halogenating agents to the 3-halo derivatives.18,34 108 253,255,294 Nitration of 2-benzyloxy-4-oxo-4H-pyrido-[ 1,2-a] pyrimidine was accompanied by debenzylation.116 Halogenation of the pyrido[l,2-a]pyrimidine (63 R = H) under forced conditions afforded the 2,3-dichloro derivatives.253,255... 

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