Bromination pyridinium ions

Figure 12.25 shows how acetals can be brominated electrophihcally because of the (weakly) acidic reaction conditions. Proper acidity and electrophihcity is ensured by the use of pyri-dinium tribromide (B). This reagent is produced from pyridinium hydrobromide and one equivalent of bromine. Pyridinium tribromide is acidic enough to cleave the acetal A into the enol ether G. This cleavage succeeds by way of an El elimination like the one encountered in Figure 9.32 as an enol ether synthesis. The enol ether G reacts with the tribromide ion via the bromine-containing oxocarbenium ion H and the protonated acetal D to form the finally isolated neutral bromoacetal C. (The reaction can be conducted despite the unfavorable equilibrium between the acetal A and the enol ether G, since G continuously reacts and is thus eliminated from the equilibrium.)... 

Rates of bromination of several methylpyridines by hypobromous acid in aqueous perchloric acid at 25°C (Table 9.9) have been measured. Rate-acidity profiles and comparison with model compounds showed that the conjugate acids were the reacting species (74JOC3481). From this work the partial rate factor for bromination of the 3-position of the pyridinium ion was estimated as 2-6 x 10 which gives a o+3 value of —2.0. 

Rf.lative Rates and Partial Rate Factors for Bromination of Pyridinium Ions"... 

Reactions of the quinolizinium ion have analogies with the pyridinium ion (see p 277/280). The quinolizinium ion as a deactivated heteroarene is resistant to electrophilic reactions. Bromination is one of the few exceptions. Firstly, it leads to the perbromide 5, then only under drastic SgAr conditions to the substitution product 6 ... 

Treatment of 2,7-di-/ert-butylthiepin (1) either directly with bromine at — 78 °C, or with pyridinium bromide perbromide at room temperature, gives the thiophene compound 2. In contrast, bromination with bromine-1,4-dioxane complex or pyridinium bromide perbromide in the presence of acetic acid leads to the thiopyran derivative 3.87 To account for these results a homothiopyrylium ion has been proposed as a common intermediate, formed by electrophilic bromination at C4 in the first step. 

For example, 3-bromopyridine is formed when pyridine is reacted with bromine in the presence of oleum (sulfur trioxide in cone, sulfuric acid) at 130 °C (Scheme 2.4). Direct electrophilic substitution is not involved, however, aszwitterionic (dipolar) pyridinium-A-sulfonate is the substrate for an addition of bromide ion. Subsequently, the dihydropyridine that is formed reacts, possibly as a dienamine, with bromine to generate a dibromide, which then eliminates bromide ion from C-2. It is notable that no bromination occurs under similar conditions when oleum is replaced by cone, sulfuric acid alone instead, pyridinium hydrogensul-fate is produced. 

Halogenation. 3-Chloroindole can be obtained by chlorination with either hypochlorite ion or with sulfuryl chloride. In the former case the reaction proceeds through a 1-chloroindole intermediate (13). 3-Chloroindole [16863-96-0] is quite unstable to acidic aqueous solution, in which it is hydrolyzed to oxindole. 3-Bromoindole [1484-27-1] has been obtained from indole using pyridinium tribromide as the source of electrophilic bromine. Indole reacts with iodine to give 3-iodoindole [26340-47-6]. Both the 3-bromo and 3-iodo compounds are susceptible to hydrolysis in acid but are relatively stable in base. 

The diene-Br2 complex is again in equilibrium with the reagents, and nucleophilic attack at carbon can be carried out either by the bromide of the ammonium bromide ion pair, formed at the moment of the electrophilic attack, or by the less nucleophilic pyridine added in excess in the reaction medium. It is noteworthy that this mechanism is characterized by a rate- and product-limiting nucleophilic step which should be quite insensitive to steric hindrance around the double bond. In agreement with a weak influence of the steric effects, pyridinium perbromide reacts in chloroform and tetrahydrofuran with substituted conjugated and non-conjugated dienes to give selectively (>95%) bromine addition to the more alkylated double bond (equation 44). 

When dissolved in tetrahydrofuran, PTT (like pyridinium hydrobromide perbromide) is a source of Brf ions, the properties of which are different from those of molecular bromine. In particular, it is much less electrophilic and less reactive toward aromatic rings and double bonds. It is thus a selective hrominating reagent for ketones or ketals - when the molecule has double bonds or activated aromatic nuclei which would be attacked by bromine. The two examples of use of this reagent clearly differentiate between its reactivity from that of bromine. Reaction of bromine with 2-acetyl-6-methoxynaph-thalene (in ether solution) gives a mixture, the main constituent of which is the product resulting only from ring bromina-tion (2-acetyl-5-bromo-6-methoxynaphthalene). ... 

The oxidation of several monohydric alcohols to the corresponding aldehydes and ketones by bis(quinuclidine)bromine(I) bromide in chloroform and in the presence of pyridinium trifluoroacetate has a two-step mechanism in which transfer of hydride ion from the substrate to the oxidant is rate-determining. The proposed mechanism is supported by the thermodynamic parameters, deuterium kinetic isotope effect, and Hammett reaction constants of the reaction. ... 

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