Bromination with pyridinium tribromide

Cyclization of enone (9) in hexane with boron trifluorideetherate in presence of 1,2-ethanedithiol, followed by hydrolysis with mercury (II) chloride in acetonitrile, yielded the cis-isomer (10) (16%) and transisomer (11) (28%). Reduction of (10) with lithium aluminium hydride in tetrahydrofuran followed by acetylation with acetic anhydride and pyridine gave two epimeric acetates (12) (32%) and (13) (52%) whose configuration was determined by NMR spectroscopy. Oxidation of (12) with Jones reagent afforded ketone (14) which was converted to the a, 3-unsaturated ketone (15) by bromination with pyridinium tribromide in dichloromethane followed by dehydrobromination with lithium carbonate and lithium bromide in dimethylformamide. Ketone (15), on catalytic hydrogenation with Pd-C in the presence of perchloric acid, produced compound (16) (72%) and (14) (17%). The compound (16) was converted to alcohol (17) by reduction with lithium aluminium hydride. 

Regioselective introduction of a bromine atom to a double bond in the substimted vinyl sugar is achieved by bromination with pyridinium tribromide and debromination with DBU (1) [55] (Scheme 3.35). -configuration of the product is expected from a specific anfi-addition in the bromination of the -alkene followed by on E2 (anfi-ehmination)... 

The intramolecular alkylation of an aryl amide by an activated bromide, readily available by bromination of a malonamide methylene with pyridinium tribromide in the substrate depicted in Scheme 39, provided an example of a type c ring closure to furnish 3-carboxymethyl-l,4-benzodiazepin-2,5-diones <20060BC510, 2002H(56)1501, 1999JOC2914>. 

Labeled a-bromomethyl derivatives can be prepared from the ketones by treatment with pyridinium tribromide elementary bromine, or CuBr2. One example of the preparation and use of such intermediates is the extension of the aliphatic side chain by two carbon atoms using the malonic ester synthesis to produce the 4-aryl-4-oxo[4- C]butyrate (7) in good yield (Figure 6.7). 

Ketones can be a-brominated on solid phase by treatment with synthetic equivalents of bromine, such as pyridinium tribromide (Entry 2, Table 6.1) or phenyltri-methylammonium tribromide (DCM, 20 °C, 3 h [10]). Resin-bound organometallic compounds, such as vinylstannanes [11] or organozinc derivatives [12], react cleanly with iodine to yield the corresponding vinyl or alkyl iodides (see also Section 3.13). Additions of halogens or their synthetic equivalents to C=C double bonds on cross-... 

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. 

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.)... 

Another way to use pyridine in brominations is to make a stable crystalline compound to replace the dangerous liquid bromine. This compound, known by names such as pyridinium tribromide, is simply a salt of pyridine with the anion Brj. It can be used to brominate reactive compounds such as alkenes (Chapter 20). 

It is known that pyridinium tribromide converts olefins with specific r/7 t/-dibromina-tion. Therefore, the v/c-dibromides thus obtained can be cathodically reduced to the original olefins without geometrical changes of molecular structure [218]. This stereospecific bromination-debromination may be useful as an olefin protection-deprotection method. 

Side-chain bromination of 5,7-dimethyl-6-aryl TPs (e.g., 187, see below) by pyridinium tribromide can be restricted to the 7-positioned methyl (06WOP34848). The same regioselectivity rule governs the reaction of 5,7-dimethyl TP (44) with DMF dimethylacetal which yields enamine 182, and, through oxime 183, nitrile 184 (Scheme 46) (96JHC465). 

These salts must be distinguished from pyridinium tribromide, obtained by treating pyridine hydrobromide with bromine, which does not contain an iV-halogen bond, but does have a trihalide anion. The stable, crystalline, commercially available salt can be used as a source of molecular bromine, especially where small accurately known quantities are required. 

Halo-, and even more so, 2-halo-indoles are unstable and mnst be utilised as soon as they are prepared A -acyl- or A -sulfonyl-haloindoles are much more stable. A variety of methods are available for the p-halogenation of indoles bromine or iodine (the latter with potassium hydroxide) in dimethylformamide give very high yields pyridinium tribromide works efficiently iodination and chlorination tend to... 

Oxidation of the 4a/7-pyrido[2,l-/][l,2,4]triazine (76) with bromine was reported <77LA1718>. The fully conjugated tribromide (77) underwent ring contraction with water to give (78) (Scheme 2). Bromination of the mesoionic (79) with pyridinium hydrobromide perbromide gave 8-mono and 8,10-dibromo derivatives. Compound (79) with DMAD afforded the tetracyclic 1 1 adduct (80) (Equation (6)) <83JCS(P1)349>. 

Elemental bromine is a popular brominating agent. However, it has significant health concerns and should always be handled with great care. An alternative brominating agent is pyridinium tribromide. While bromine is a liquid, pyridinium tribromide is a solid and... 

A wide variety of aromatic compounds can be brominated. Highly reactive ones, such as anilines and phenols, may undergo bromination at all activated positions. More selective reagents such as pyridinium bromide perbromide or tetraalkylammonium tribromides can be used in such cases.18 Moderately reactive compounds such as anilides, haloaromatics, and hydrocarbons can be readily brominated and the usual directing effects control the regiochemistry. Use of Lewis acid catalysts permits bromination of rings with deactivating substituents, such as nitro and cyano. 

Pyridinium hydrobromide perbromide salt was introduced by Djerassi and Scholz as an alternative brominating agent to bromine in 1948. Salazar and Dorta rationalized that since alkylpyridinium salts are well documented and commercially available room temperature ionic liquids, a combination of an alkylpyridinium cation with tribromide anion 1 should therefore lead to a room temperature ionic liquid bromine analogue (Equation 1). 

Bromination also can be carried out with reagents that supply bromine in the form of the Br anion. One such reagent is pyridinium bromide tribromide. Another is tetrabutylammonium tribromide. These reagents are believed to react via the Brj-alkene complex and have a strong preference for anti addition. 

---